Lactofen Case 7210 www.regulations.gov D ocket Number EPA-HQ-OPP-2005-0287 Pesti c ide Re-evaluation Division



## Lactofen Proposed Interim Re gist ration Review Decision



## Proposed Interim Registration Review Decision Case Number 7210 July 2014

App ro ved by: 

# \!'-S?

# ~ --Q.s--**~** Director Pesticide Re-evaluation Divi sion
Date:

# ~\\**zcN\**Lactof en Case 7210 www . regulations.gov Docket Number EPA-HQ -OPP -2005-0287 Pesticide Re- evalu at ion Division



### Ta b l e of Contents Pro posed Interim R egistration Review D ecisio n

I. Intro ducti on ...... . ... .................. . ............ .. ........ ... .. ..... . ...... . ...... . .. .. .. . ... . ... . .. . ................ ) II. Use and Us age .. . . .. .. .. .. . ... . ... . . ............................................................... . .. .. .. . ... . .. .. .. .. . 4 III. Scientific Asses sments
.............................. ... . .. . .. .. .. ..... ......... .. . .. .. . ... ........................ 

### .4 

### TV
. Propos e d Inter i m Registration Rev i ew Decision
................................................... 15 V
. Next Steps and T imeline
. . ... .. . .. ....................................................... .. .......... . . ......... 1 5

2Lac tof en Case 72 10 www . regulations.gov D ocket Num b er EPA-HQ- O PP- 200 5-0 287 Pes tic ide Re

- e val uat io n Di vis io n I. INTRODUCTION Proposed Int e rim Regis tra ti o n R evi ew Decis ion

This document is the Env ironmental Protection Agency ' s (EPA or the Agency) Propos e d Interim Reg is tration Re v i ew D ec ision for lactofen (PC code 128888) and is being issued pursuant to 40 CFR sect i on s 15 5 .56 and 155.58. A registration review decision is the Agency's determination whether a pestici de meets, or does n ot me et, the standard for registration in the Federal In secticide, Fun gicide , an d Rodenticid e Act (FIFRA). T he Agency may issue, when it determines it to be appropriate , an interim registration revi ew decision b efore comp let ing a registration review. Am o n g other things , the interim registratio n review decision may: 1) require new risk miti g ation measures ; 2) impose interim risk mit igat ion measures ; 3 ) identify data or information required t o co mplete the review ; and 4) include schedules for submi tt ing the required data , conducti ng the new risk assessment and completing the registration review
. For further information on lacto fen, additional documents can b e found in EPA's public docket (EP A -H Q-OPP-2005-0 2 87) at www.regulation s .gov. FIFRA, as amended by t h e Food Qu ality Protecti on Act (FQPA) of 1996 , mandat ed the continuou s review of ex i st ing p esticides. All pesticides distrib u ted or sold in th e United States ge nerall y must be registered by the EPA based on sc i entifi c data showi n g that they will not cause unreasonable risks to human health or to the e nvironment when u sed as directed on product labeling. The registration rev iew program is intended to make s ure that, as the ability to assess and reduce risk evolves a nd a s policies and practices change , all registered pesticides continue to meet the statutory stand ard o f n o unreasonable adverse effect s . Changes in scienc e , public policy , and pesticide us e pract ices will occur over time. Through the registration review program, the Agency periodically re-evaluates pesticides to make s ure that as these changes occur, products in th e marketplace can continue to be u sed safe ly . Informati o n on this program is provided a s www.epa. gov/o opsndllregi s tration review /
. In 2006 , the Age nc y implemented the re g istration re v ie w program pur suant to FIFRA section 3 ( g) and will re vi ew each registered pe s ticide every 15 years to determine whether it continues to meet the FIFRA s tandard for regi stration. Lacto fen was first registered in 1987, and the refore wa s not subj ect to reregistration because it wa s registered after N ovember 1984. Pur s uant to 40 C FR 

### § 155.50, the Ag e ncy formally initiated registration review for l actofen (case 7210). The following highlights significant events that have occurred during the reg i strat io n review of lactofen and can be found in public docket (EPA -HQ -OPP-2005-028 7 , accessed at www.regu l ation s . g ov):

• February 2 , 2007

- Publ ication of th e La c tofen Summar y Docum e nt for a 60-day public comment per i o d
. The Summary Docum ent included th e Preliminar y W o rk Plan (PWP) and was accompanied by the scoping document and problem formulation.

• July 16 , 2007

- Final Work Plan (FWP) for lactofen was issued
. Three comments were 

### received but 

### they did not 

### modify the PWP.



### 3Lactofe n Case 7210 www . rt:gu Iat i on s .gov Docket Number E PA-1-J Q-O PP-200 5-0287 Pes ti cide Re-ev alu ation Divi sion Proposed Interi m Registration Review Decisio n

• September 18 , 2009- Generic Data C all-In ( GDCI ) for lactofen was issued.

• March 20, 20 I 3

- The Agency published th e Preliminary Envir onmental Fa te and Ecological Risk Assessm e nt in Support of the Registration Review of Lactofen and the La ctofe n - Occupational Exposure /

Risk Assessment for Lacto fen Use on Soybe an , Snap Bean, Strawberr y (Non -Be aring) , and Conif er Seedlings for a 60-day pu b lic comment per i od. No comments we re recei ved durin g the comment period
.
• J uly 20 14

- T he Agency is now publishi n g the Lactofen Proposed Interim Registration R eview Decision , in do cke t numb er E PA-HQ-OPP-2005-0287 for a 60-day pub lic comment period
. 

### II
. USE AND USAGE Lactofe n i s a light dep ende nt pero xidizing herb icide ( LDP H)
. LDP H s are a class o f weed control chemi cal s that act in p lants by inhibiting the enzyme proto p orphyr inogen ox idase (protox), which i s the last com mon enzyme in the heme and chlorophyll biosynthetic pathway s. Protox exists in both plants and animal s , and t he e nzyme from both sources has been s ho w n to be se nsitive to many LD PHs. L acto fen is regis tered for u se on soybe an , cotton, peanut s, conif e r s eedlin gs, and kenaf. It also ha s sta te
- speci fie (Florida) uses on s nap beans, fruiting vegetables, and okra. Soybeans and peanut s are the dominant use pattern s for lactof e n , repres enting approxi mate ly 99% of the total estim a ted acre s t reated annually with lactofen in the U.S. Data indicate th at th e largest u se of lactofen is on soybeans, both in term s of absolute number of acres treated ( 1 million) and the proportion of the total ac res treate d with lactofen in the U.S (95%). For more inf ormat io n on the us e an d u sage o f lactof e n , see Use/ Usag e Refinem en t in Support of Regi s tration Review of Lactofen (1 28888) , dated April 15 , 2014, in the public d ocket (E PA

- HQ-OPP

- 2005-0287) which can be accessed on http: //www.reg ul ations.gov/
. 

### III. SCIENTIFIC ASSESSMENTS A. Human Health Assessment A summ ary of the Agency's h um an health ri s k asses s ment is p rese nted b e low. Fo r detailed discussions of all aspects of the human health risk assessment, see L ac to fen

- Occupati onal Expos u re /Risk A ssess ment for Lactofen Use on Soybe an, Sn ap B ean, Strawberry (N on-Bearing) , and Con ifer Seedlings, date d J uly 16 , 20 1 2; Lactofen Summary Do c ument, dated J anuary 2007 ; and Lact o fen: Human Health Risk Assessment for Pr oposed Uses on Fru iting V

eget a bles and Okra, date d January 8, 2007, in the public docket (EPA-HQ-OPP-2005

- 0287) whic h can be accessed on http: //www.regu lati ons.gov/.

4Lactofcn Case 721 0 www.regulations.gov Docket Number EPA-HQ-OPP-2005-0287 Pest icide Re-evaluation Divi sio n 1. Summary Of R isk Estimates Dietary Exposu re Prop osed Interim Registration R eview Dec ision

As indicated in the La ctofen Summa!y Document, the Agency dete rmined that previously completed dietary assessments for lactofen are adequate and there are no dietary risks that exceed the Agency's level of co nce rn (LOC). For food al one and food plu s water , all exposures were less than 1% ofthe acute and chronic popul ation adjusted dose (aPAD and cPAD). Resid e ntial Exposure

T here are no residential uses for lactofen. Therefore, the Agency determined a re sidential assessment was not nec ess ary . Aggregate Exposures As stated above , there are no re s idential uses for lactofen , so an aggregate assess ment would only include food and drinking water assessments. As previously mentioned, the Agency has determined there are no di eta ry risks that exceed the Agency's LOC, with all exposures less than 1% ofthe aPAD and cPAD. ln the Lactofen: Human Health Risk Assessment for Proposed Uses on Fruiting Vegetables and Okra document , the Agency also conducted aggregate risk assessments for acifluorfen, which is an environmental degradate of two registered herbicides, lactofen and sodium acifluorfen. Therefore, an aggregate ass essment was required for acifluorfen considering exposures from both ac tive in gredie nts. The assessment included food exposure from to lerance level residues fro m sod ium acifluorfen applications, resid e ntial handler exposure f rom spot treatments of sod ium aciflu orfen , and drinking water exposure to acifluorfen as a re sult of envi ronmental degradat ion of lactofen. The aggregate assessments for all exposure durat ions were below the Agency 's level of concern, with the acifluorfen assessments at 6% ofthe aPAD. Short-term aggregate risk was not a concern, with a margin of exposure (MOE) equal to 16 , 000, whic h exceed s the targ ets MOE of 1 ,000. Long-term aggregate risk for acifluorfen was also not a concern, with the mo s t highly exposed subgroup (infants less than one year old) at 37% of the cPAD. Cumula ti ve Effects Section 408(b)(2 )( D )(v) of the Federal Food, Dru g, and Cosmetic Act (FFDCA) requires the Agency to consider the cumulative effec ts of exposure to lactofen and other substances that have a common mechanism of toxicity. These consi d erations i nclude the possible cumulative effects of such residue s on inf ants and children. Lactofen is a member of the diphenyl ether group of herbicides, as are sod ium acifluorfen and oxyfluorfe n. Ho wever, EPA has not made a common mechanism oftoxicity finding for lactofen for these compounds a nd other substances.

5Lactofen Case 72 10 www.reg ul ations.gov D ocket umbe r EPA-HQ-OPP-2005-0287 Pestici de Re-evaluati o n Division Occupational Exposure Proposed Interim Registration Review Deci sion

As indicated in the Lactofen

- Occupational Exposure /

Risk Assessment for Lactofen Use on Soybean, Snap Bean, Strawberry (Non-Bearing), and Conifer Seedlings document, the Agency has determined that there is a potential for short- and intermediate-term dermal and inhalation occupational ex posure to l actofen during handling activities, such as mixing, l oading, and application. However, none of the occupational handler exposure scenario s that were assessed resulted in combined dermal and inhalation risks of concern (MOEs J ess than 300) , with either baseline attire, with the addition of chemical-resistant gloves, and/or engineering controls , such as enclosed cockpi ts and cl osed mixing/loading systems for aerial applications, which are currently required on the applicable labels (MOEs range from 400 to 6,200). The Agency also determined that there is a potential for agricultural workers to have post-application dermal exposure to Jactofen following use on soybeans and conifer seedlings when those workers re-enter p reviously treated areas. Howe ver, there were no risks of concern associated w ith these p ost-app li cation handler exposure scenarios (MOEs range from 680 to 1,500). 

### 2. Human Incidents As indicated in t he Lactofen: Human H e alth Risk Assessment for Proposed Uses on Fruiting V ege tables and Okra docu ment , in 2006 , the Agency reviewed the poisoning incident data on lactofen in the following databases: OPP Incident Data Systems (IDS) , P oiso n Control Centers, California Department of Pesticide Regulation, National Pesticide Information Center (NPIC), and National In stitute of Occupational Safety and Health's Sentinel Event Notification System for Occupationa l Risks (N IOSH SENSOR). There were few report s of ill effects from exposure to lactofen in the available databases. No recommend ations could be made based on the limited availability f or lactofen. 

### 3. Food Toleranc es U.S. food tolerances are listed under 40 CFR 180.43 for lactofen. No tolerance reassessment was nece ss ary at this time. 

### B. Ecological Assessment For non-listed species , the Agency identified no risk concerns for freshwater and terrestrial invertebrates
. Howe ver , potential risks were identified for non-listed fish (and aquaticphase amphibians) , estuarine / marine invertebrates , aquatic non-vascular plants , mammals, birds , reptiles , terrestrial-phas e amphibians, and terrestrial plants (d i cots)
. These ri sks are summarized below. For detailed di scussio n s of all aspects of the environmental risk asse ssment , see t he Preliminary Environmental Fa te and Ecolog ical Risk Assessm en t in Support of the Registration Review ofLactofen, pub li s hed o n March 20 , 2013 in the publi c docket (EPA-HQ-OPP-2005- 0287) which can be ac cessed on http: //www.regulations.gov/
.

6Lactofen Case 721 0 www.r<;:gu l ations.gov Docket Number EPA-HQ-OPP-2005-0287 Pesti c ide Re-ev aluation Division Proposed Interim Registration Review Decision
The Agency also completed a screening-level endangered and threatened (listed) species assessment for lactofen and identified potential risks to fish (and aquatic-phase amphibians), estuarine/marine invertebrates , aq uatic non-vascular plants, mammal s, birds, reptiles , terrestrialp hase amphibians , and terrestr ia l non-target plants, particularly dicot s . The Agency is currently working with its federal counterparts and other stakeho lders to implement an interim approach for assessing potential risk to listed species and their de signated critical hab itats. Once the scientific methods necessary to complete risk assessments for listed and species and their designated critical habitats are finalized, the Agency will comple te it s endangered species assessment for lactofen. As such, only screeni ng -level risks to l isted species will be e numerated here. Risks to listed species will not be characterized herein. 

### 1. Environmental Fate and Exposure Lactofen degrades quickly when released into the environment, primarily via aerob i c soil metab olism and hydrolysis. Lactofen is not persistent (ha lf-life le ss than 3 days) in the environment, has a high affini ty for binding to soil, and low solubility. Lactofen is not expected to leach to ground water because of its high binding pote nti a l and short half-life
. Lactofen is transported off si te primarily thro u gh spray drift but also throu gh erosio n ; however , lactofen is likel y to degrade before the eroded soil particles runoff from the application site. Lactofen is expected to read il y degrade in both terrestrial and aquati c environments under ae robic and anaerobic cond itions, and is cons idered slightly to hardly mobile, and nonvolatile. Lactofen is not persistent in so il, with half-lives ranging from 1 to 3 days in aerobic soil and hal f

lives of 45 days in an aerob ic soil. Lactofen also degrade s readily by hydrolysis and photolysis, with half-lives for both less than 21 days in environmentally re l evant conditions. Lactofen does not bioconcentrate in aquati c organisms
. Lactofe n is expecte d to di ss ipate through spray drift, erosion an d via rapid degradation. The environmental de gradate of lacto fen that is co nsidered to be of exposure concern is acitluorfen, which is also registered as a unique pesticide active ingredient (PC code 1 1 4402). Thi s degradate fonne d at incre as ing con centrations through the environmental fate studies, and was still present at study termination
. Thi s degradate is more persistent an d more mobile than the parent lactofen with comparable toxicity, and is therefore the primary exposure concern re lativ e to lactofe n use . Aquatic exposure estimates for lactofen are based on the exposure of th e parent compound lactofen only. Estimates for acitluorfen exposure due to lactofen use are estimated separately. These es timate s were made due to acitluorfen's high persist ence and mobility re lative to lacto fe n. Terrestrial animal exposure estimates are based on the res idue levels of lactofen and ac i tluorfen. The formation of aci tluorfen is conservativel y assumed to be 64% of the parent lactof en based on the maximum relative occurrence in envi ronment a l fate studies, however, it is 50% by molecular weight. T errestrial plant exposures are based on pare nt lacto fen alone.

7Lactofen Case 7210 www.reg,ulation s.gov Docket Number EPA-HQ-OPP-2005-0287 Pe st i c ide Re-evaluation Division Proposed Interim Registration Review Decision


### 2. Ecological Exposure and Summary of Risk Estimates Risk to Aquatic Organisms Effects to Freshwater Fish (surrogatefor Aquatic -Phase Amphibians) and Estuarine/Ma rine Fish Ri sk Quotients (RQs) for freshwater fish (surrogate for aquatic-phase amphibians) (RQs range from 0.001 to 0.00 4 ) and estuari ne/marine fish ( RQ range from < 0.012 to <0.031) for a ll uses of lactofen fall below the Age ncy's acute risk to lis ted (0.05) and non-listed (0 .5 ) spec i es LOCs. Therefo re , risk to freshwater and estuarine / marine fish is not expected on an acute exposure basis. However , as s tated above , LDPHs are a class of weed control chemicals that act in plants by inhibiting protox which exists in both plants and animals. The enzyme in both plants and animals has been show n to be hi ghly sensitive to many LDPHs. Several studies have docume nted enhanced toxicity of LDPHs to fis h in the presence of u V light comp ared to tox ici ty observed under standard labo ratory lighting. Given that aquatic o rganisms are likely to be exposed simultaneously to LD PH and u V light in natural settings, concerns have been raised that g uidelin e chroni c exposure laboratory tests may underestim ate the toxicity of LDPH in the field. In the absence of chemical

- specific data on LDPH toxicity und er enhanced u V li ghting and until toxicity testing being conducted by the LDPH task force is complete, the Agency i s applying an in terim adjustme n t factor of29X to adjust the no observed adverse effect concentration (NOAEC ) values to accoun t for the pote nti al enhanced toxicity of LDP H c h emicals under natural sunlight. This enhanced sensitivity to LDPHs is not necessarily limited to aquatic fish and could be observed in other taxa; however , the Agency is only applying the adjustment factor to fish at this time. Chroni c exposure RQs for fish we re calculated with and w i thout the 29X adjustment factor. RQs for fish that may not receive high-intensity u V light ran ge f rom 0.08 to 0.25, and are below th e Agency ' s LOC ( 1 ). Howe ver, the RQs for fish with the LDPH adjustment factor range from 2.33 to 7.12, and exceed the LOC (1) up to 7-fold. Therefore, there are potential ef fect s to fish (and aquatic-ph ase amph ibians) from chronic ex posure to l actofen. Effects to Freshwater and Estuarine /

Marine Invertebrates Acute RQs for fres hw ate r i nvertebrates (<0.01) and estua rine/ m arin e in verte brates (RQs range from 0.035 to 0.096) do not exceed the acute LOC for non -li sted species (0.5). However , the LOC for acute effects to listed estuarine/marine invertebrates (0.05) is exceeded, with an R Q as high as 0.096. There are no chronic data for f reshwater invertebrate s, but the estuarine / marine acute endpo i nt is two orders of magnitude lo we r than the freshwater ac ute endpo int. While an acuteto-chronic ratio (ACR ) can be applied , i t wou ld result in RQ s ord ers of magnitude l ower th an the estuarine / marine e ndpoint. Ba sed on the estuarine/ marine acute endpoint, there are no chronic LOC (1) exceedances for aquatic invertebrates , as the highest RQ is 0.12. At this t ime, the Agency is not applying th e 29X facto r to aquati c inverteb r ates, an d therefore the ri sk assessment does not indicate a potential for chronic risk to aquatic i n verteb rates.



### 8Lactofen Case 7210 www.regulat i ons.gov Docket Number EPA-HQ-OPP-2005-0287 Pesticide Re-evaluation Division Effects to Aquatic Plants Proposed Interim Registration Review Decision

RQs for non-listed aquatic vascular plants ranged from 0.03 to 0.07, RQs for listed aquatic vascular plant s ra nged from 0.1 to 0.27, and neither exceed the LOC (1). As a result , there is insufficient exposure to lactofen for the LOC to be exceeded for aquatic vascular plants. RQ s for non-listed aquat ic non-vascular plants ranged from 1.36 to 3.70 and exceeded the LOC (1 ). As a result , there are risks of concern for aquatic non-vascular plants through exposure to lactofen. · Risk to Terrestrial Organisms Effects to lvfammals Acute RQs were not calculated for mammals because only non-definitive acute oral toxicity data were availab l e. Based on th e avai l ab l e acute toxicity data, no mortality was observed in any of the mammalian studies conducted on lacto fen technical or its formulated products at the highest concentrat ions/ doses tested. Chronic risk to mammals from lactofen is indicated on both a dose and dietary basis
. Based on the currently labeled maximum application rates, there are exceedances of the chronic LOC ( 1) for chronic dose

- based exposure for mammals of all size classes for all use patterns (RQs range f rom 0.42 to 37.48)
. Additionall y, there are exceedances of the chronic LOC ( 1 ) for chro nic dietary-based exposure ( RQs ran ge from 0.11 to 4 .32). There are no acute exceedances for mammal s based on the degradate acifluorfen exposure , as all RQ s are _::::0.02. At the common soybean/cotton application rate, there are no chronic exceedances (RQs range from 0.03 to 0.92) of the LOC (1). At the highest rate (Florida f ruiting vegetab le s), the L OC ( 1 ) is exceeded (RQs range from 1.07 to 2.34). The conifer seedl ing use also exce eds the LOC (1) for s mall mammals consumi n g short grass (RQ is 1 .1 4). Effects to Birds, Reptile s, and Terrestrial-Phase Amphibians Acute RQs were not calculated for birds, repti l es, and terrest ri al -phase amphibians because only non-defin i tive acute and sub-ac ute toxic ity endpoints were available. Bas ed on the currentl y labeled maximum application ra tes, th ere is chro ni c dietary-based exposure exceedance o f the LOC (RQ=1.61 for the Flo rida fruiting vegetable and okra use pattern). No other use pattern has an RQ> 0.79. H owever, the ac ifluorf e n degradate exhibits greater toxicity to birds than the parent, lacto fen. There were exceedances of the chronic LOC ( I) for all use pattern s for birds feeding on short grass (RQs ranged from 1 .20 to 3.07). RQs also exceeded the LOC ( l) for two uses (Florida fruiting vegetables and okra and Oregon strawberries) for tall grass (RQs were 1.41 and 1.05 , respectively) and broadleaf plants / small insects (RQs we r e 1
.73 and 1
. 28, respectively).

9Lac to f e n Cas e 7210 www . r e gulations.gov Dock e t Numbe r EPA-HQ-OPP-2005-0287 Pe s ti c ide Re-evaluation Division Proposed Interim Regi s trati o n R ev iew Deci s io n Effects to T e rrestrial Invertebrates Both lactofen and acifluorfen are classified as practically non-toxic to hon eybees on an acute exposure basis. Only non-defi ni ti ve endpo i nts are availabl e a nd RQs were not calculated. Based on the low toxicity of lactofen on honeybees, no risks of concern are indicated to terre strial invertebrates. However this assumes that the other insect taxa a re similarly unaffected by lactofen and acifluorfen exposure. Effects to Non-target T e rrestrial Plants As expected with an he rbicide, risk to non - target plants is indicated. Based on the available data, monocots are les s sensitive to lactofen than dicots, and generall y vegetat ive vigor i s a mo re se ns i ti ve li fe

- stage than seedli n g e mergence. For bot h aerial and grou nd applications the LOC (1) for both l isted and non - listed plants is exceeded fo r dicots in semi-aquatic areas (RQs range from 5
. 10 to 57.47) and for most inhabiting dry areas (RQs range from 0.60 to 10.45). Monocots inhabi ti ng semi-aquatic areas result in exceedances at higher rates (0.25, 0.38, and 0.512 lbs ai/ A) (RQs ranged from 1.06 to 2.17). RQs base d on spray drift al one exceed the LOC (l) for dicots fo r all rate s for both aerial (RQs ranged from 5.56 to 46.55) and ground (RQs ranged from 1.11 to 9.3 1) applications. RQs for monocots for drift alone do not exceed the LOC (1) (RQs range f r om < 0.1 to 0
. 58 )
. 

### 3. Ecological Incidents A review of the Ecological Incident Information System (EllS) database for incidents involving lactofen and the acifluorfen de gradate was conducted on January 25, 2012. Four incidents for lactofen are reported in the database. Of these, three are p lant i ncidents that occurred from use on agricultura l areas. The fourth incident i n volved mortali t y of an unkno wn numbe r of unspecified fish. However , this incident was deemed to be unlikely. T here was one reported incident f or acifluorf e n from a registered use (as an active ingredient) on beans (likely soybeans). This incident also reported mortality to an unknown number of unspecified fish species, and was also deemed to be un likely. Similarly , a search of t h e Avian Incident Monitoring System (A IMS; http ://www.abcbird s .org/ abcpro gr arn s /policy/toxins/ airn s/ aims/ index.cfm) was conducted on J anuary 25,2012. AI MS i s a d atabase adm in istered by the American Bird Conservancy that contains pub li cly available data on reported av i an i ncidents involving pesticides. No incidents involving lactofen or aci fl uorfen were found. Pesticide registrants report certain types of incidents to the Agency as aggregate counts of i ncidents occurring per product per quarter. One aggregated plant incident has been rep orted to the Agency associated with lactofen, in the summer of 2000. Unless further information regarding this ag g regate incident is disco vered , it will be assumed that it resulted from registered use. There were 43 aggregate p lant incidents reported for acifluorfen between 1995 and 2003. However, since the risk asses sment is not cons i de ri ng terrest ri al plant exposure to acifluorfe n , these incidents will not be cons i dered further.

10Lactofen Case 7210 www. regulation s .gov Docket Number EPA -H Q-OPP

-2005-0287 Pe s t ic ide Re-evalu a tion Divi sion Proposed Interim Registrati o n Review Deci s ion C. Risk Characterization 1. Human Health Ri s k All human health exposure pathways con sidere d for lactofen based on its registered use patterns, i .e., dietary (food an d drinking water) , agg regate, and occup at ional handl ers, did no t res ult in ri s k esti m ates that exceeded LOCs. Therefore, no characterization of human health risks is necessary. 2 . Ecological Ris k EPA has determ i ned that there i s potential for adverse e f fec ts t o non-listed fis h (and aquatic-ph ase amphibi ans ), estuarine/marine invertebrates , aquatic non-vascular plants, mammal s , birds, rept il es, terrestrial-pha se amphi bians , and terrestrial plants (dicots)
. Uncerta inties R e garding Ecological Ri s k Althoug h the Agency has determined that there are potential ris k s to certain taxa, there are areas of uncertainty in regards to the Agency ' s ca l culation o f risk of lacto fen to the affected taxa . Th ese uncertainties inclu de:
• For chronic risk to mamm als, a 35 d ay default foliar dissipation half-life w as use d to calculate R Qs. In some fate stud ies , lactofen is shown to degrade mu ch more qu i ckly. To addre ss this uncerta inty , RQ s were modeled u s ing a hypothetical three day half-life
. Use o f a three day half-life results in a 40% reduction in the RQs (e.g
. , 14.64 to &.6 6). Th erefo re, using a more accurate half-life wo uld likely reduce the RQ s for mammals, b ut a dissipation study would be needed t o acquire these data. However, even if data were available to reduce the foliar dissipation half-life used i n the mode l , RQs would still like ly exceed th e LOC
.
• Moreover , there are no chroni c RQ e xceedance s for risk to mammals from the degradate acifluorfen in all sce narios , except for the Flo rid a fruiting vegetable use , whe re avai lable us e and usage data suggests there i s little to no actual use, and one sce nari o for the conifer seedlin gs use (RQ 

### = 1.14 ). For more inform at ion on available u se and u s age data, p lease see t h e Use and Us age Information section below.

• Addi tion ally, for chronic ri sk to mammal s, the highe st RQ s (e.g., 37.48 ) we re calculated usi ng th e maximum a pplication rates for Florid a fruiting v egetab le s and Orego n st rawberri e s . As stated above, th e re is li ttle to no u se of lactofen o n Fl o rida fruiting vegetables , and the strawberry use has been voluntarily cancell ed by the registrant (70 FR 1 3 76), effective January 8 , 2014. When re m ov ing these rates, th e next hi gh est maximum rate , fo r conifer see dling s, res ults i n RQs le ss than half of those estimated fr om the Florida fruit in g vegetable use (e.g. , 18
. 30).

• For chronic risk to fres hwater and estuarine/ marin e fish, the 29X interim adjustment fac tor due to lactof e n being an LDPH causes the RQ s to exceed the Agency's LOC.

11Lactofen Case 7210 www . rcg ulations
. go v Docket Number EPA-IIQ-OPP-2005-0287 Pesticide Re-evaluation Division Proposed Interim Registration Review Decision
Not all fish w ould be expected to be exposed to both I acto fen and high u V light at the same time, but it ha s not yet been determined what conditions might mitigate the effect. It would seem reasonable to assume that fish inhabiting shallow , clear water bodi es would be more susceptible to chronic effects than those in deeper , more turbid water bodies. Also, fish inhabiting water bodies at lower elevations or higher latitudes may also be less likely to exhibit chronic effects due to uV -enhanced toxicity. The Agency also reali zes many other factors can impact the amount ofuV light , such as time of day, time of year , stratospheric ozone and weather (cloud cover).

• RQ s are a co n servati ve estimate of risk in that EPA selects the most sensitive toxicological effect f r om all available ecotoxicity studies. Avail able ecotoxicity studies often indicate less toxicity to te st species than is assumed in EPA 's screeninglevel assessments. The toxicity endpoint used in risk assessment is chosen to represent a w o rst case toxicity scenario. 3. Other Considerations Although there are estimated risks which exceed the LO C for certain taxa , the Agency considers multiple lines o f evidence when making a risk management decision. EPA has taken into account data on lac tofen-specific use patterns that provide a more accurate picture of !actofen use in the field. Addi t ionally, data is available on the benefits of using lactofen in different crop systems to meet certain needs. Ple ase see below f or more details. Use and Us age Informa tion There are several factors f rom available use and usage information that have been gathered and outlined b el ow. For more information on th e use and usage information, please see Use / Usage Refinement in Support of Registration Review of Lactofen (128888) , dated April 15, 2014.

• Da ta suggest that the actual ac reage of crops in the United States treated with lactofen is very min i mal. The use and usage report indicates that less than 1% of soybean acreage is treated with lactofen. This 1% (approximate ly 1 million acres) represents 95% of the total acre s treated w ith lactofen annually in the U.S. For peanuts, the next largest lactofen crop, percent crop treated is less than 2.5% (approximately 42,000 acres), accounting for approximately 4% of the annual totallactofen treated acres in the U.S. Therefore, soybean and peanuts together represent approximately 99% of the total ac res treated with lactofen annually in the U.S.

• Additionally , data suggest that average application rate used by growers for soybeans is 0.12 lbs. a.i./acre , whereas the ecological risk assessment used the maximum application rate of 0.2 lbs. a. i./acre. Moreover , the average application rate used by growers for peanuts is 0.17 lbs. a.i ./ acre , whereas the ecological risk assessment used the maximum application rate of 0.2 lbs. a.i ./ acre.

12Lactofen Case 7210 www. regulati ons.gov Docket Number EPA-HQ-OPP-2005-0287 Pe sticide Re-evaluation Division Proposed Interim Registration Review Deci s ion



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### • Data suggest there is little to no use of lactofen on several crops that were identified as drivers in the ecological risk assessment, such as Oregon s trawberrie s and F lorida fruiting vegetables. Lactofen use on Florida fruiting vegetables is registered under FIFRA 24 (c), Special Local Need (S LN ). EPA proprietary data , which includes use of SLN products, show no usage for Florida fruiting vegetables for 1998-2012, suggesting little or no lactofen use on Florida fruitin g vegetables. Additionally, the state
- specific use o f s trawberries was voluntarily cancelled by the regi stran t (70 FR 1376), effecti ve January 8 , 20 14. From a bene fi ts standpoint, lactofen may be used as a tank-mix partner with g lyphosate in soybeans to manage several spec ie s of glyphosate-resistant weeds , suc h as kochia and common waterhemp. Additionally , in no-till soybean production, lactofen may be us ed as a burn-down treatment against g l yphosate -resistant waterhemp. Lactofen also provides a wider window of herbicide application than many other herbicides and can be applied as a pre-p l ant pre- emergence or a postemergence tre atmen t. With this use and usage information , combined with the conservative nature of the risk a ss essment and the aforementioned unc ertainties, the Agency does not believe that potent ial ecological risks are of concern from the regis tered uses of lactofen
. 

### 4. Endange r ed Species Assessment In November 2013, the EPA, al ong with the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Servi ce (NMFS) (collectively, the S e rvices) , and the U.S. Department of Agriculture (USDA) releas e d a summary of their joint In terim Approaches for assessing risks to listed species from pesticides. The Interim Approaches w ere developed jointly by the agencies in response to the National Academy of Sciences' (NAS) recommendations and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. The NAS rep ort outlines recommendat ions on spec ific scientific and tec hnical issues related to the developm e nt of pesticide risk assessments that EPA and the Services mu st conduct in connection with th eir obligations under the Endangered Species Ac t (ES A) and FIFRA. The joint Interi m Approaches were released prior to a stakeh older workshop held on November 15 , 2013. In addition , the EPA presented the joint Interim Approaches at the December 20 13 Pe sticide Pro gram Dialo gue Committee (PPD C ) and State-FIFRA I ssues Research and Evaluation Grou p (SFIREG) meeting s, and he ld a stakeholder workshop in April 20 14 , allowing additional opportunities for stakeholders to comment on the Interim Approaches. As part of a phased, iterative process for developing the Interim Approaches, the agencies will also consider public comments on the Interim Approaches in connection with the development of upcoming Registration Review decisions. The details of the j o int Interim Approaches are conta ined in the white paper " Inte rim Approaches for National-Level Pesticide Endangered Species Act Assessment s Bas ed on the Recommendations of the National Academy of Sciences April2013 Report, " dated November 1, 2013.

13Lactofen Case 72 10 www.regulaticm s .gov Docket Number EPA-H Q-OPP- 200 5-0287 Pesti c ide Re-evalu ation Divi s i on Proposed Interim Registration Review Deci s ion
Given that the age ncie s are continuing to develop and work toward implementation of the Interim Approache s to ass ess the potential risks of p esticides to listed species and the ir designated c ritical habitat, the eco logical risk assessment supporting thi s Proposed Interim Registrat ion Review D ecis ion for lactofen does n ot co ntai n a com plet e ESA anal ysis that includes effects determi n a tions for specific listed species or d es ignated critical habitat. Although EPA h as not yet comp let e d eff ec ts determinatio n s for spec ific spec i es or hab i tats , for this preliminary ass essment EPA conducted a scree nin g- level as sessment for a ll taxa of no n - target wildlife and plants that ass umes for the sake of the assessme nt that listed spec ie s and designated critical habitats may be presen t in the vicinity of th e appl i cati on of !actof e n. This sc ree ni ng -l e vel assessment will a ll ow EP A to focus its future evalu ations on the types of spec i es where the pote nt ial for effects exis ts once the scientific methods being developed by the agencies have been fully vetted. Onc e t he agencies hav e fully developed and imple me nted the scientific me thods n eces sa ry to complete ri sk asse ss ments for e ndangered and threatene d (l is ted) spec i es and their designated c riti cal h abitats, these methods will be applied to subsequent a nalyses for lactofen as part of comp l et ing this registration review. 5. Endocrine D isruptor Screening Program As required by FIFRA and FFDC A, EPA reviews numero us studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studie s in cl ude ac ute, subc hroni c and chronic t oxicity , including assess ments of carcinogenicity , neurotoxicity, developmental, reproductive, and general o r system ic toxicity. These stu die s include endpoints which may be susceptib le to endocrine influence , including effects on e ndocrine target organ hi sto patho l ogy, o r gan weights , es trus cyclicity, sexual maturati on, fertility , p regnancy rates , reproductive loss, and sex rati os in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic s tudies that assess growth, developmental and re producti ve ef fect s in di fferent taxonomic groups . As part of its most recent registration deci s ion fo r l actofen, E PA reviewed these data a nd selected the mo s t se nsitiv e endpoints for relevant risk ass ess men t scenarios from the exist ing hazard database. Ho wever, a s requ ired by FFDCA sect io n 408(p) , lac to fen is su bject to the endo cri ne screening part of the End ocr ine Disrupter Screening Program (EDS P ). EP A ha s de ve loped the EDS P to determine w hether certa in substances (in c luding pesticide act ive and other ingred ients) may have an eff ect in humans or wildlife similar to an effec t produce d by a "naturall y o ccurrin g est rogen , o r other such endocrine effec ts as the Ad mini strator may designate." The ED S P employs a two-tiered approach to makin g the statutoril y req uired determinations. Tier I co nsists of a battery o f 11 screening assays to ide nti fy th e po tent ial of a c h emical s u b stance to interact with the estrogen, andro ge n , o r thyro id (E, A, or T) hormon al system s. C hemi cal s that go through Tier 1 scree ning and are found to have the potential to interact w it hE, A, or T hormonal systems will proceed to the next sta ge o f the EDS P where EPA will determin e which, if an y, of the Tier 2 tests are necessary based on the avail ab le data. T ier 2 testing is desi gned to identify any adver se endocrine-re l ated effects caused by th e substance , and establis h a dose-response relationship between the dose and the E , A , or T effect. Under F FDCA s ection 408(p), th e Agency must screen all pesticide chemicals . Betwee n October 2009 and February 201 0, EPA issue d test orders/data call

- ins for the first g roup of 67

14Lactofen Case 7210 www.regulations.gov Doc k et Number EP A-I-I Q-OPP-2005-0287 P

es ticide Re-eva l uation D ivision Proposed Interim Registrati on Review Deci sio n chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of c hemic al s ide ntifi ed for EDSP screenin g was published on June 14, 2013 1 and includes some pesticides scheduled for Regist ration Review and chem i cal s found in water. Neither of t hese lists should be construed as a list of known or likely endocrine disrupters. For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test gui d e line s and th e Tier 1 screeni ng battery, please visit our website. 2 Lacto fen is on Lis t 2. Li st 2 represents the next set of chemicals for which EPA intends to issue test orders/ data call-ins in the near future. In the interim, EPA is making no human health or environmental safe ty findi ng s associated with the EDSP screen ing of lactofen. Before completing this regi stration re view, the Agency will make an EDSP FFDCA section 408(p) determination. 

### IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION In acco rdan ce w ith 40 CFR Sections 155.56 and 15 5.58, the Agency is issuing this Proposed Interim R egistration Review Decision. Except for the EDSP and ESA components of this case , the Age ncy has made the following Propo se d Interim Registration Review Decision: (1) the Agency does not believe that potential ecological risks are of concern from the registered uses of lactofe n , when taki ng into account the use and usage information and uncertainties outlined above, combined with the conservative nature of the risk assessment; (2) potential human health ri sks due to lactofen exposure are be low the Agency's LOCs ; (3) no add ition al data are required at this time; however, submission of a foliar diss ip ation study to the Agency would help to determine a more appro pri ate half

- life fo r lactof en, and provide more rep resentative risk est imates; and (4) changes to the affected registrations and their labeling are not needed at this time. In this proposed interim registration review decision, EPA is making no human health or environmental safety findings asso ciated with the EDSP screening of lactofen , nor is it making a comp le te endangered spe cies finding. The Agency's final regi st ration review decision for lactofen will depend upon both the re sul t of an ESA Section 7 cons ultation with the Servic es, and an EDSP FFDCA s ection 408(p) determination. 

### V. NEXT STEPS AND TIMELINE A. Interim Registration Review Decision In acco rdan ce with 40 CFR sections 155.56 and 155. 58, the Agency is issuing th is proposed interim registration review decision document, and placing it in the lactofen registration review do cket (EPA-HQ-OPP-2005-0287) for public comment for 60 days. A Federa l Register Notice will anno unce the availability of this proposed interim registration review decision for I acto fen and initiate a 60 -day public comment period. If th ere are no

l See http://www.regulations .gov /#!do cumentDetail;D=EPA -HQ

- OPPT-2009-047 7-007 4 for the final second l ist of chemicals. 2 http://www.epa.gov/endo/

15Lactofen Case 7210 "ww.regulations.gov Docket Number EPA-HQ-OPP-2005-0287 Pe s t i cid e Re-evaluation Di vision Propo sed Interim Reg is tration Review Deci s ion

s ignificant comments or additional information submitted to the docket during the comment period that leads the Age ncy to change its proposed decision, EPA will issue an interim registrat ion review deci sio n fo r lac tofen (case 721 0). B. Implementa tion of Mitigation Measures As stated in Secti on IV , no mitigation measures are required for Iacto fen at this time.



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