Lactofen Case 7210 "'' w.r..:gulations.gov Docket Number E PA-H Q

- OPP

- 2005-0287 Pesticide Re

-evaluation Division Inte ri m R egistration Review Decisio n



# Lactofen Interim Registration Review Decision Case Number 7210

Approved by:



### Date: 

# December 2014



# G C-hcy..pl 

## P

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# ,'J-) Richard P. Keigwin, 

### Jr. Director Pesticide Re-evaluation Di v isionLactofen Case 7210 "1\\\ .r.:gulations.gov Docket Number EPA-HQ-OPP-2005-028 7 Pesticide Re

- evaluation Di vision



### Tabl e of Contents Interim Registrati o n Rev iew Decision

I. Introd u c tion ................................ . ............ . . .. ..... . . . . .. .................... . .. .. . .. . ... .. .. . ... .......... ] II. Use an d Usage
. . ... .. .. .. . .. .. .. ... . ... . ........ .. ........ . .. .. .. . .. .. ..... . ... . .................. . ........ .. .. .. .......4 II I. Sc ienti fic Assessments .......................... . ........... . . .. ............................... . .. ... . . ... .. .......4 IV. Interi m Reg i strati on Re v iew Decision
........ . . ... . ... . .. .. . ...... . ......................... . . ... .. . .... 1 5 V
. Next S t eps and Time li ne .. . ... . ..................... . .............. . .................. . .. . .. . ..... .. ............ 1 5



### 2Lactofen Case 7210 ""'"
. rt!gulat io nS.I!.OV Doc k et Number EPA-HQ- O PP-2 005-0287 Pesticide Re

-evaluation Division I. INTRODUCTION Interi m R egistrati on R eview Deci s ion

This docum en t is the Environmental Protecti on Agency's (EPA or the Agency) Interim Registration Review Decision for lactofen (PC code 128888) and is being issued pursuant to 40 C FR sections 155.56 and 155.58. A registration review decision i s the Agency's determination whether a pesticide meets , o r does not meet, the standard for registration in the Federal In secticide, Fungicide , and Rodenticide Act (FIFRA ). The Agency may i ss ue, when it determines it to be appropriate , an interim registration review decision befor e completing a regis tration revie w. Among other things , the interim registration review deci s ion may: 1) require new risk mitigation meas ures; 2) impose interim ri s k mitigation measure s; 3) identify data or information required to complete the review ; and 4) include schedules for s ubmitting the r equire d data, conducting the new risk assessment and completing the re g istr ation review. For further information on lac to fen, additional documen ts can be fo und in EPA's
.public docket (EPA

- H Q-0 PP- 2005-0287) at www.regulation s .gov . FIFRA , as amended by the Food Quality Protection Act (FQPA) of 19 96 , mandated the continuous rev iew of ex i s ting pesticides. All pesticides dis t ributed or sold in the United State s ge ne rally must be regi s te red b y the EPA based on scientific data showing that they will not cause unrea so nable risks to human health or to the envi ro nment when used as dire cted on product labeling. The regist rat ion review program is intended to make sure that, as the ability to assess and reduce risk evo l ves and as policies and practic es change, all registered pesticides continue to meet the statutor y s tandard of no unreasonable advers e effects. Changes in sc ienc e, public policy, and pesticide use practices will occur over time. Through the re g is tr at ion review program , the Agency p e riodically re-evaluate s pesticides to make sure that as these changes occur, products in the marketplace can continue to be used safely. Informati o n on this program is pro v ided as www.epa.gov/ o ppsnd I/registration review /
. In 2006, the Ag e ncy implemented the registration review program pursuant to FIFRA sec tion 3(g) and will rev iew each registered pe s ti cide every 15 years to determine whether i t continues to meet the FIFRA standard for registration. Lactofen was first registered in 1987, and therefore was not subject to reregistration because it was regi s tered after Novemb er 1984. Pur suant to 40 CF R 

### § 155 .50, the Agenc y fo rmally initiated r egistration review for lactofen ( case 721 0 )
. The following bullets highlight significant events that have occurred du rin g the registrati o n rev ie w of lactofen and can be found in public docket (EPA-HQ-OPP2 005-0287, accessed at www.regulations.gov):

• February 2, 2 007

- Publication of the L ac to.f e n Summary Docum ent fo r a 60-day public comment period. The Summary Document included the Preliminary Work Plan (PWP) and was acco mpanied by the scoping document and problem formulat ion
.
• July 16 , 2007 -F inal Work Plan (FWP) for lactofen was issued. Three comments were received but they did not modify the P WP.

3Lactofen Case 72 1 0 www. r l!gu l ations.gov Docket umber E PA-HQ- OPP

- 2005-02 87 Pesticide Re-evalu a tion Division Interim R egistr ati on Review Decision

• September 18, 2009

- Generic Data Call-In Notice (GDC I) for lac tofen was issued.

• March 20, 2013

- The Agency published the 

### Pr eliminary Environmental Fate and Ecological Risk Assessment in Support of the Registration Re v iew of Lac tofen and the 

### Lactofen- Occupational Exposure /

Risk Assessment for Lactofen Use on Soybean, Snap Bean, Strawberry (Non-Bearing), and Conife r Seedlings for a 60-day pub li c comment period. No comments were received du rin g the co m ment period.

• Jul y 23 , 2014- The Agency published the 

### Lactofen Proposed Interim R egistration R ev iew Deci s ion for a 60 -da y publi c comment period. The Agency rec eived two comments; one from the Center for Biological Diversity , and one from the registrant, Val ent Corporation.

• December 20 1 4 -The Agency is now publishing the 

### Lac to

fen Interim Registration Rev iew Decision. This document , and those found above and after can be found in docket number EPA- HQ-OPP- 2005-0287 at www. regul at ions.go v. Public Comments During the 60

- day public comment period on the Lac tofen Proposed In terim Registration Review D ecision, which opened on July 23,2014 and closed on September 22 , 2014, the Agency received two submissions ; one from the Center for Biological Diversity , and one from the registrant , Valent Corporation. The Center for Biological Diversity ' s comment addressed the Agency's responsibilities under the Endangered Species Act (ESA). Vale n t's comment addressed the methodo logy and endpoints used in drafting the eco logica l preliminary ri s k assessment. Neither comment resulted in a change in the proposed interim decision for lactofen. The Age ncy has summarized both comments and has provided its responses below. Both comments can be found in their entirety in docket number EPA-HQ-OPP- 2005

- 0287 at W\.YW.regulations.gov. Comment s ubmitt ed by the Center for Biological Diversity in EPA -HQ-O PP -2005-028 7- 0027. Comment: 

### The Center for Biological Div ersity's (CBD) comments focus on the EPA's independent duty under th e Endangered Species Act (ESA) to consult with the U.S. 

### Fish and Wildlife Service and the Nat ional Marine Fisherie s Service (the Servi ces) on the registra ti on rev iew of /a cto fen. Agency Response: EPA has re viewed the comments f r om CBD on the regi s tration review docket openin g for lactofen and plan s to address many of the concerns rai sed by CB D as part of the implementation plan for assessing the risks of pesticides to li sted species based on the recommendations ofthe April2013 National Academy of Sciences (NAS) report. EPA will address concerns specific to lactofen in connection with the development of its registratio n re v iew decision for lactofen.
4Lactofen Case 7210 www.n:gulations.!!OV Docket Number EPA-HQ-OPP-2005-0287 Pesticide Re-e valuati on Division Interim Registration Review D ecisi on

In November 2013 , the EPA, along with the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS) (collectively, the Services), and the U.S. Department of Agriculture (USDA) released a summary of their joint Interim Approaches fo r assess i ng risks to listed species from pesticide s. The Interim Approaches were deve l oped 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 address ing scientific differen ces between the EPA and the Services. TheNAS repo 1 t outlines recommendatio ns on specific scient ific and technical i ssues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the Endange red Species Act (ESA) and FIFRA. The joint Interim Approaches were released prior to a stakeh older workshop held on November 15, 2013. In addition, the EPA presented the jo int Interim Approaches at the December 2013 Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues Research and Evaluation Group (SFIREG) meeti ngs, and held a stakehol de r workshop in April 2014 , allowing additional opportunities for stakeholders to comment on the Interim Approaches. A s 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 Regi str ation Review decision s. The details of the joint Interim Approaches are contained in the white paper "Interim Approaches for National-Level Pesti c ide Endangered Species Act Assessment s Based on t h e Recommendations of the National Academy of Sciences April 2013 Report," dated November I, 2013. Given that the agencies are continuing to develop and work toward impl ementation of the Interim Approac h es to assess the potential ri s k s of pesticides to listed species and their designated critical habitat, the ecological ri sk assessme nt supporting this I nter im Registrati on Review Deci sion for lactofen does not contain a complete ESA analysi s that includes effects determinations fo r specific listed species or designated critical habitat. A lthough EPA has not yet comp leted effects determinati ons for specific spec i es or habitat s, for this preliminary assessment EPA conducted a screening-leve l assessment for all taxa of non - target wild li fe and plants that as s ume s for the sake of the assessment that listed species and designated critical habitats may be present in the vicinity of the application of lactofen. This screening level assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists once the scientific metho ds being developed by the agencies have been fully vet t ed. While the agencies continue to develop a common method for ESA analysis, the re gulatory section of the Interim Registration Revi ew Decision document will describe the lev e l of ESA analysis completed fo r this particular re gistrat ion review case. Once the agenc ies have fully developed and implemented the scientific methods necessary to complete risk a ssess ments for endangered and threatened (listed) species and their designa ted critical habitats , these methods will be applied to s ubsequent analyses for lactofen as part of completing this registration review.

5Lactofen Case 7210 www.regu lat ions . gov Docket Number EPA

- HQ-OPP-2005-0287 Pesticide Re-e v aluati o n Division Interim Registrati on Review D ecision
Comment submitted by Valent Corporation in EPA -lJQ - OPP -2005-0287-0028. Comment: 

### Valent ' s comments focus on th e EPA's ecological preliminar y risk assessment en titled " Preliminary En vironmental Fate and Ecological Ri s k Assessment in Support of the Regis tration R eview of Lactofen ", dated March 13, 2013, which can befound in the public docket in EPA-HQ-OPP-2005-0287-021. Valent makes numerous comments critiquin g the Agency's risk assessment models and procedures, as well as seve ral other specific commen ts pertaining to endpoint selectio n and the potential risk.findings spec!fic to lac tof en identified in th e risk assessment. Agency Response: The Age ncy thanks Valent for its comments. EPA notes that the exposure assessment metho ds , too l s, and ass umptions used in the preliminary risk assessments have evolv e d over time and have been we ll documented and peer reviewed. Where appropriate, th e Agency will consider Valent's general methodolo gica l comments as noted. For more detailed and specific responses to Valent 's comments , please refer to the document enti tled , 

### "Respo nse to Comments Regarding th e Lactofen Regis tration Review Pre liminary Risk Assessment That Were Submitted During Registration Review Proposed Interim Decision Public Comment P eriod', dated December 2, 2014, which can be found in the p ublic docket at www.reg ulations.gov. II. USE AND USAGE Lactofen is a light dependent peroxidi z ing herbicide (LDPH). LDPH s are a class of weed control chemicals that act in plants by inhibiting the enz yme protoporphyrinogen oxidase (pro tox), which is the las t common enzyme in the heme a nd chlorophyll biosynthetic pathway s. Protox exists in both plants and animals, and the enzyme from both sources has been shown to be sensitive to many LDPHs
. Lactofen is regis tered for use on soybean , cotton , peanuts, conifer seed lin gs, and kenaf. It also ha s sta te-spec ific (F lorida) uses, registered under FIFRA sec tion 24 (c), on s nap beans , fruiting vegetab les, and okra. Soybeans and peanut s are the dominant use patterns for lactofen , representing approximately 99% of the total estimated acres treated annually with lactofen in the U .S. D ata indicate that the largest use of lactofen i s on soybeans ; both in term s of absolute number of acres treated ( 1 million) and the proportion of the total acres treated with lactofen in the U.S (95%). For more in fo rmation on the use and usage of lactofen, see 

### Use / Usage Refinement in Support of Regis tration Review of Lactofen (128888) , dated April 15,2014, in the public docket (EPA

- HQ-OPP-2005

- 0287) which can be acce sse d at www.regulations.gov. III. SCIENTIFIC ASSESSMENTS A. Human Health Assessment A summary of the Agency's human health risk assessment is presented below. For detailed discussions of all aspects of the hum an health risk assessment, see 

### Lactofen

- Occupational Exposure /Ri s k Assessment for Lactofen Use on Soybean , Snap Bea n, Strawberry (N on - Bearing), and Con ifer Seedl ings, dated July 16, 2012 ; 

### La ct ofen Summary Document, dated



### 6Lac to fen Case 72 I 0 www .regu lations.gov D ocket Nu mber E PA-HQ-OPP-2005

- 02 87 Pesticide Re-evaluati o n Divisio n Interim Registration Review Decision January 2007; and 

### Lactofen: Human Health Risk Assessment for Proposed Uses on Fruiting Vegetables and Okra, dated January 8, 2007 , in the pub li c docket (EPA

- HQ-OPP-2005 -0287 ) which can be accessed on http: //www.regu l ations.gov/. 1. Summary Of Risk Estimates 

### Dietary Exposure A s indicated in the 

### Lactofen Summar y Document, the Agency determined that previously com pleted dietary assessments for lactofen adequately characterize the hazard and exposure of lactofen and there are no dietary risks that exceed the Agency 's level of concern (LOC). For food alone and food plus water, all exposures were less than I% of the acute and chronic population adjusted dose (aPAD and cPAD). 

### Residential Exposure There are no residential uses for lactofen. Therefore, a residential assessment was not necessary. 

### Aggregate

**Exposur~s** A s stated above , there are no residential uses for lactofen , so an aggre gate assessme nt would only include food and drinking water exposures . As prev iously menti oned, the Agency has determined there are no dietary risks that exceed the Agency's LOC, with a ll expos ures le ss than 1% of the aPAD and cPAD. In the 

### Lactofen: Human Health Risk Assessment for Proposed Uses on Fruiting Vegetables and Okra document , dated Janu ary 8 , 2007 , the Agency also cond ucted aggregate risk assessments for acifl uorfen , which is an environmental de gradate of two registered herbicide s, lactofen and sod ium acifluorfen. Therefore, an aggregate assessment was required for acifluorfen cons iderin g expos ures from both active ingredients. The asse ssment included food exposure from toleranc e level residues from sodium ac ifluorfen applications , residential handler expo sure from spot treatments of sodium acifluorfen , and drinking water exposure to acifluorfen as a result of environmental degradation of lacto fen. The aggreg ate assessments for all exposur e durations were below the Agency 's level of concern , with th e acifluorfen exposures at 6% of the aPAD. Short-term aggregate risk was not a conc ern, with a margin of exposure (MOE) equal to 16,000, which exceeds the targets M O E of I ,000. Long-term aggregate risk for acifluorfen was also no t a concern, with the most highly exposed subgroup (infants Jess than one year old) at 37% of the cPAD. 

### Cumulativ e Effe cts Section 408(b)(2)(D)(v) of the Federal Food, Dru g, and Cosmetic Ac t (FFDCA) requires the Agency to consi der th e cumulative effects of exposure to lactofen and other su bstances that have a common mechanism o f tox icit y. These considerations include the possible cumulative effects of such residues on infant s and children.

7Lactofen Case 72 10 \\ ww.ro::gulati o n s.gov D ocket Number EPA-HQ-OPP-2 005

- 0 287 Pe s t icide Re-evaluati on Division Interim Regi s tration R eview Decision 

## •
Lactofen is a member of the diphenyl ether group of herbicides, as are sod ium acifluorfen and oxyfluorfen. Howe ver, EPA has not made a common mechanism of toxicity finding for lactofen or the se other subs tance s. 

### Occupational Exposure As indicated in the 

### Lactofen

- Occupational Exposure /

Risk Assessment for Lactofen Use on Soybean, Snap Bean, Strcnvberry (Non-Bearing), and Conif e r Seedlings document, dated July 16, 2012 , the Agency has determined that there is a potential for short

- and intermediate -term dermal and inhalation occupational exposure to lactofen during handling activities , such as mixing , loading, and app li cation. However , none of the occupational handler expos ure scenarios resulted in combined dermal and inhalation risks of concern (MOEs less than 300) , with either baseline attire, with th e addition of chemica l-resistant gloves , and / or engineering controls, such as enclosed cockp its and closed mixing / loading systems for aerial applications , which are currently requ ired on the applicable label s (MOEs range from 400 to 6,200). The Agency also determined th at there is a potential for agricultural workers to have post-application dermal exposure to lactofen fo ll owi ng us e on soybea ns and con if er seedli n gs when those workers re-enter previously treated areas. Howev er, there were no ri sks of concern associated with these post-application handler exposure scenarios (MOEs ran ge from 680 to 1,500 , with a LOC ofMOEs less than 300). 2. Human Incidents As indicated in the 

### Lactofen: Human Health Risk Assessment for Proposed Uses on Fruiting Vegetables and Okra document , dated January 8 , 2007, the Agency reviewe d the poisoning incident d ata on lactofen in 2006 , in the fo llowin g databases: OPP Incident Data Systems (IDS) , Poison Control Centers, California Department of Pesticide Regulation, National Pesticide In forma tion Center (NPIC), and National Institute of Occupa tiona l Safety and Health 's Sentinel Event No tificati on System for Occup ational Risks (NIOSH SENSOR). There were few report s of ill effects from exposure to lactofen in the available databases. No recommendations could be made based on the limited availability for lactofen. 3. Food Tolerances U.S. food t o lerances are li sted under 40 CFR 180.43 for lac to fe n. No tolerance reassessment was necessary at this time. B. Ecological Assessment For non-listed species, the Agency identified no risk concerns for freshwater and terrestrial invertebrates. However, potential risks were identified for non,.li sted fish, estuarine /marine invertebrates , aquatic non-vascular plants , mammals, birds, reptiles, terrestria lphase amphibians, and terrestrial plants (d icots). These risks are summari zed below. For detailed discussions of all aspects of the environmental ris k assessment, see the 

### Preliminaty


### 8Lactofen Case 721 0 www.n:gulations.gov Docket Number EPA-HQ-OPP-2005-0287 Pes ticide Re-evaluation Division Interim Registration Review Decision
Environmental Fare and Ecological Ri sk Assessment in Support of the Registration Review of Lactofen, dated March 13,2013 , which can be found in the public docket (EPA-HQ -OPP-2005- 0287) which can be accessed on http: //www.regulations.gov/
. The Agency also completed a screening-level endangered and threatened ( li sted) species assessment for lactofen and id ent ified potential risks to fish, estuarine/marine invertebrates, aquatic non-vascular plants, mammals, birds, reptiles, terrestrial-phase amphib ian s, and terrestrial non-target plants, particularly dicots. The Agency is currently workin g with its federal counterparts and other stakeholders to implement an interim approach for assessing potential risk to listed species and their designated critical habitats. Once the scientific methods necessary to complete risk assessments for listed and species and their designated critical habitats are finalized, the Agency will complete its endangered species assessment for lactofen. As such, only screening-l evel risks to listed species will be enumerate d here
. Risks to listed species will not be characterized herein. 1. Environmental Fate and Exposure Lactofen degrades quickly when released into th e environment, primarily via aerobic so il metabolism and hydrolysis. Lactofen is not persistent (half-life les s than 3 days) in the environment, has a high affinity for binding to soil, and low solubility. Lactofen is not expected to leach to ground water because of its high binding potential and short half-life. Lactofen can b e tra nsported off site primarily through spray drift and also through erosion; however, lactofen is likel y to degrade before th e eroded soil particles runoff from the applica tio n s ite. Lactofen is exp ected to readil y degrade in both terrestrial and aquatic environments under aerobic and anaerobic conditions, and is considered slightly to hardly mobile, and nonvolatile. L actofen is not persis tent in soil, with half-lives rangin g from 1 to 3 days in aerobic so il and halflives of 45 days in anaerobic soil. Lactofen also degrades readily by hydrolysis and photolysis, with half-lives for both less than 21 days in environmentally relevant conditions. Lactofen does not bioconcentrate in aquatic organisms. Lactofen is expected to dissipate through spray drift , erosion and via rap id degradation. Due to a lack of data , a 35-day defau lt foliar dissipation halflife was used. The environmental de gradate of lactofen that is co ns idered to be of exposure concern is acifluorfen, which is also registered as a unique pesticide ac tive ingredient (PC code 114402). This degradate formed at increasing concentrations throu gh the environmenta l fate studies, and was still present at study termination. Thi s degradate is more persistent and more mobile than the parent lactofen with comparable toxicity, and is therefore the primary exposure concern relative to lactofen use. Aquatic exposure estimates for lactofen are based on the exposure of the parent compound lactofen only. Estimates for acifluorfen exposure due to lactofen use are estimated separately. These est imate s were made due to acifluorfen's high persistence and mobility relative to lactof en.



### 9Lactofen Case 7210 \\· ww.regulation s.gov Docket Number EPA-HQ-OPP-2005-0287 Pesticide Re-evaluation Division Interim Registration R ev iew Decision
Terrestrial animal exposure estimates are based on the residue levels of lactofen and acifluorfen. The formation of acifluorfen is conservatively assumed to be 64% of the parent lactofen based on the maximum relative occurrence in environmental fate studies, however , it is 50% by molecular weight. Terrestrial plant exposures are based on parent lactofen alone. 2. Ecological Exposure and Summary of Risk Estimates Risk to Aquatic Organisms Effects to Freshwater Fish (surroga te for Aquatic-Phase Amphibians ) and Estuarine /Marine Fish Risk Quotients (RQs) for freshwater fish (surroga te for aquatic -phase amphibians) (RQs range from 0.001 to 0.004) and estuarine/marine fish (RQ range from <0
. 0 12 to < 0.031) for all uses of lactofen fall below the Agency's acute risk to listed (0.05) and non-li s ted (0.5) species LOCs. Therefore, risk to freshwater and estuarine/marine fish is not expected o n an acute exposure basis. H owever, as stated above, LDPHs are a class of weed contro l chemicals that act in pl ants by inhibiting protox which exists in both plants and animals. The enzyme in both plants and animals has been shown to be highly sensitive to many LDPH s. Several studies have documented enhanced toxicit y of LDPH s to fi s h in the presence of u V light compared to toxicity observed under standard laboratory lighting. Given that aquatic organisms are likely to be exposed simultaneously to LDPH and u V light in natural settings, concerns hav e been raised that guideline chronic exposure laboratory te sts may un dere stim ate the toxicity of LDPH in th e field. In the absence of chemical-specific data on LDPH toxicity under enhanced u V lighting and until toxicity testing being conducted by the LDPH task force is complete , the Agency is applying an interim adjustment f actor of29X to the no observed adverse effect concentration (NOAEC) values to account for the potential enhanced toxicity of LDPH chemicals under natural sunlight. This enhanced sensitivity to LDPHs is not necessari ly limited to aquatic fish and could be observed in other taxa; however , the Agency is only applying th e ad jus tment factor to fish at this time. Chronic exposure RQs for fish were calculated with and without the 29X adjustme nt factor. RQs for fish t hat may not recei ve high-intensity uVlight range from 0.08 to 0.25, and are below the Agency's LOC (1 ). However , the RQs for fish with the LDPH adjustment factor range from 2.33 to 7 .1 2, and exceed the LO C ( 1 ) up to 7

- fold. Therefore, there are potential effects to fish (and aquatic-phase amphibians) from chronic exposure to lactofen. Effects to Freshwater and Estuarine /Marine Invertebrates Acute RQs for freshwater invertebrates (<0.01) and estuarine /marine invertebrates (RQs range from 0.035 to 0.096) do not exceed the acute LOC for non-listed species (0.5). However , the LOC for acute effects to li sted estuarine / marine invertebrates (0.05) is exceeded (RQ = 0.096). There are no chronic data for freshwater inverteb rates, but the estuarine /ma rine acute endpoint is two order s of magnitude lower than the freshwater acute endpoint. While an acuteto-chronic ratio (AC R ) can be applied, it would result in RQ s orders of magnitude lower than the

10Lactofen C ase 7210 www .r. :gul ation s. gov Docket umber EPA-HQ-OPP-2005-0287 Pesticide Re-evaluation Division Interim Registration Re view Decision
estuarine/marine endpoint. Based on the estuarine/marine acute endpoint , there are no chronic LOC (I) exceedances for aquatic invertebrate s, as the highest RQ is 0.12. At this time, th e Agency is not applying the 29X factor to aquatic invertebrate s, and therefore the risk assessment does not indicate a potenti a l fo r chronic risk to aquatic invertebrates. Eff ec ts to Aquatic Plants RQs for non-listed aquatic vascular plants ranged from 0.03 to 0
. 07, RQs for listed aquatic vascular plants ran ged from 0.1 to 0.27 , and neither exceed the LOC (1). As a result, there is in sufficient exposure to lactofen for the LOC to be exceeded for aquatic vascular plants
. RQs for non-bsted aquatic 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 lactof en. Ri sk to Terrestrial Organi sms Eff ec ts to Mammals Acute RQs were not ca lculated for mammals because only non - definitiv e acute oral toxicit y dat a were av ailabl e. Based on the available acute toxicity data, no mo rtality was observed in any of th e mammalian studies conducted on lactofen technical o r it s formulated products at the highest concentrations/doses tes ted. Chronic risk to mammals from lactofen i s indicated on both a dose and dietary basis. Based on the c urrently labeled maximum application rates, there are exceedance s of the chronic LOC ( I ) for chronic dose-ba se d exposure for mammals of all s ize classes for all use patterns (RQs ran ge f rom 0.42 to 37.48). Additionall y, there are exc eedances of the chronic LOC (1) for chronic dietary-based expo s ure (RQs range from 0.11 to 4.32 ). There are no acute exceedances fo r mammals based on the degr adate acifluorfen exposure , as all RQs are _:::0
. 02. At the common soybean/cotton applica tion rate , there are no chronic exceedances (RQs range from 0 .03 to 0.92) of th e LOC ( 1). At the hi ghest rate (Florida fruiting vegetables), the LO C 

### (I) is exceeded (RQs range from 1.07 to 2.34 )
. The conifer seedling use also exceeds the LOC (1) for small mammals con s uming short grass (RQ is 1.14)
. F;f(e c ts to Birds, Reptiles, and Terre s trial-Phase Amphibians Acute RQs were not calculated for birds, reptiles , and terrestrial-phas e amphibians because onl y non-definiti ve acute and sub-acute toxicity endpoints were available. Bas ed on the current ly labeled maximum app lication rates , there i s chronic dietary-based exposure exceeda nc. e of the LOC (RQ=I.61 for the Florida fruiting vegetable and o kra use pattern). No other use pattern has an RQ > 0.79. However , the acifluo rfen de g r adate exhibits greater toxicity to birds than the parent, lactofen. There were exceedances of the chron ic LOC (1) for all use patterns for birds feeding on sho rt g rass (RQs ranged from 1.20 to 3.07). RQ s also

I lLac tofen Case 7210 www .r egu lations.gov Docket Number EPA-HQ-OPP-2005-0287 Pe s ticide Re-evaluation Divis ion Interim R egis tration R ev i ew Decision
exceeded the LOC (I) for two uses (F lorida fruiting vegetables and okra and Or egon strawberr ies ) for tall grass (RQs were 1.4I and 1.05, respectively) and broadleaf plants/ small insects (RQs were 1.73 and 1.28, respectively). 

### Effects to T errestrial In vertebrates Both lactofen and acifluorfen are classified as practi cally non-toxic to honeybees on an acute exposure basis. Only non-definitive endpoints are available and RQs were not caiculated. Based o n the low toxicity of lacto fen on hone ybees, no risks of concern are indicated to terrestrial invertebrates. However this assumes that the other insect taxa are similarly unaffected by lactofen and acifluorfen exposure . 

### Effects to Non-target Terrestrial Plants As expected with an herbicide, ri sk to non-target plants is indicated. Based on the available data, monocots are less sensiti ve to lactofen than dicots, and generally vegetative vigor is a more sensitive life-s tage than seedling emergence. For both aerial and ground applications the LOC ( I) for both listed and non-listed p lants is exc eede d for dicots in semi-aquatic areas (RQs range from 5.10 to 57.47 ) and for most inhabitin g dry areas (RQs range from 0.60 to I 0.45). Monocots inhabiting semi-aquatic areas result in exceedances at higher rates (0 .25 , 0.38, and 0.5 12 lbs ai/ A) (R Qs ranged from I.06 to 2.17). RQs based on spray drift alone exceed the LOC (1) for dicot s for all rate s for both aerial (RQs ran ged from 5.56 to 46.55) and ground (RQs ranged from 1.11 to 9.31) applications. RQs for monocots for drift a lone do not exceed the LOC (I) (RQs range from <O .I to 0.58). 3. Ecological Incidents A review of the Ecological Incident Inf ormation System (Ell S) database for incidents involving lactofen and the acifluorfen degradate was conducted on January 25, 20 I2. Four incidents for lactofen are r eported in the database. Of these, three are plant incidents that occurred from u se on agricu ltural areas. The fourth incident involv ed mortali ty of an unknown number of unspecified fish. However, this incident was deemed to be unlikely. There was one reported incident for acifluorfen from a registered use (as an active in gredient) on beans (likel y soybeans). This incident also reported mortality to an unknown number of unspecified fish species, and wa s also deemed to be unlikely. Similarly , a sea rch of the Avian Incident Monitoring System (AIMS; http: //www.abcbirds.org/abcprog rams / polic y/ tox i ns/ aims/ aims / index.cf in) was conducted on January 25, 2012. AIMS is a database administered by the American Bird Conservancy that contains publicly avai lable data on reported av ian incidents involvin g pesticide s . No incidents involving lactofen or acifluorfen were found. Pesticide registrants report certain types of inciden t s to the Agency as aggregate count s of incidents occurrin g per product per quarter. One aggregated plant incident has been reported to the Agency associated with lactofen, in the s ummer of2000
. Unless further information regarding this aggregate incide nt is discovered , it will be assumed that it resulted from registered

12Lac t o fen Case 721 0 "\\ \\ .rt:gulations.gov Docket Number EPA-HQ-OPP-2 005-02 87 Pest icide Re-e valuation Division Interim Registrat i on R eview Deci sion

use. There were 43 aggregate plant incidents reported for acifluorfen between 1995 and 2003. However, since the risk assessment is not considering terrestrial plant exposure to acifluorfen, these incidents will not be considered further. C. Risk Characterizatio n 1. Huma n Health Risk All human health exposure pathways considered for lactofen based on its registered use patterns , i.e., dietary (food and drinking water) , aggregate, and occupational handlers , did not result in risk estimates that exceeded LOCs. Therefore, no characterization o f human health risks is necessary. 2. Ecologica l Risk EPA has determined that there is potential for adverse effects to non-l is ted fish (and aquatic-phase amph ibians) , estua rine/marine invertebrates, aquatic non-vascular plants, mammals, birds, reptiles, terrestrial

-phase amphibians, and terrestrial plants (dicots). 

### Cons iderations Regarding Estimated Ecological Risk A l though th e Agency has determined that there are potenti al risks to certain taxa , there are areas of uncertain ty in regards to th e Agency's calculation of risk oflactofen to the affected taxa. These uncertainties include:

• For chronic risk to mammals , a 35-day default fo liar dissipation half-life was used to calculate RQs. In some fate studies , lactofen is shown to degrade much more quickly. To address this uncertainty, RQ s were modeled using a hypothetical three day half-l i fe. Use of a three day half-life results in a 40 % reducti on in the RQs (e.g., 14.64 to 8.66). Using a verified half-life would li ke ly result in re d uced RQs for mammal s. Therefore, the Agency intends to require a non-guid eline fo li ar diss ipation study at this time.

• Additionally , for chronic risk to mammals , the highest RQs (e.g., 37.48) were calculated using the maximum application rates for Florida fruiting vegetables and Oregon strawberries. As stated above , there is little to no use of l actofen on Florida fruiting vegetables. Additionally, the strawberry use has been vo luntaril y cancelled by the registrant (70 FR 1376), effective January 8, 2014. When removing these rates, the next highest maximum rate, for conifer seedlings, re s ult s in RQs less than h alf of those est imated from the Florida fruiting vegetab le use (e.g., 1 8
. 30), but still in exceedance of the LOC.

• Given that lactofen degrades quickly (one to three days) in the environment via aerobi c s oil metabolism, potential chronic risk exposure is likely to come from acifluorfe n rather than the parent lactofen. There are no chronic RQ exceedances for risk to mammals from the degradate acifluorfen in all scenarios (RQs range from 0.03

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### •

• to 0.92), except for the Florida fruiting vegetable use (where available use and usage data suggests there is little to no actual use) and one scenario , sma ll mammal s eat in g short gr ass, for the conifer seedlings u se (RQ 

### = 1.14). For more in format ion on available use and usage data, please see the Use and Usage Informat ion section below. For chron i c risk to freshwater and estuarine /mar i ne fish , the 29X i nterim adjustment factor due to lactofen being an LDPH cau ses the R Q s to exceed the Agency ' s LOC. Not all fish would be expected to be exposed to both lactofen and high 

### u V light at the same time, but it has not yet been determined what condition s might mitigate th e effect. It would seem reaso nable to assu me that fish inh abiting s hallow, clear water bodies would be more susc eptible to chronic effects than those in deeper, more turbid water bodies. Al so, fish inh abiti n g water bodies at lower e levati ons or higher lat itudes m ay also be less likely to exhib it chronic effects due to 

### u V-enhanc ed toxicity. At hi gher latitudes , the sun is lower in the sky, so uV li ght must travel a greater d is tance through o z one-rich portions of the atmosphere , and therefore expose those latitudes to less u 

### V radiation. Alternately, u 

### V intensity dec reases with lower elevation because there is more atmo s phere to absorb u Vrays. The Agency also · realizes many other facto r s can impact the amount of u Vli ght , such as time of day, t ime of year , str atospheri c ozone and weather (cloud cover). Therefore, chro nic RQ estimates for fres hwater and estuarine/marine fish assoc i ated wi th the interim adjustment factor are uncertain. 

### 3. Other Conside r atio ns Although th ere are es timated risks which exceed the LOC for certain taxa, the Agency cons ide rs multiple lines of evidence when making a ri sk management deci s ion
. EPA has taken into account data on lactofen

- spec ific use patterns that provide a more accurate picture of lactofen use in the field. Addi ti onally, data are ava ilable on the benefits of using J acto f en in differen t crop sys t ems to mee t certain needs. Please see bel ow for more detai ls . Use and Usage Information There are several facto rs from av ailable u se and usage information that have been gathered and outline d below. For more information on the use and usage info r mation , please see Use / Us age Refin eme nt in Support of Registration Rev i ew of Lactofen (128888) , dated April 15, 2014.
• D ata suggest th at the ac tual acreage of crops in th e U ni ted States treated w ith lactofen i s very m i nima l. The use and usage report indicates that less than 1 % of soybean acreage is treated with lactofen. Thi s I % (approxi matel y 1 million acres) represents 95% of th e total acres treated with lactofen annually in the U.S. For peanuts , the next largest lac tofen crop , percent crop tre ated is less than 2.5% (approximately 42 ,000 acres ), account ing for approximately 4 % of the annual total lactofen treated acres in the U.S. Therefore, soybean and peanuts together repre sent approximately 99% of

14Lactofen Case 7210 ww\\' .rcgul a tion s.gov Docket Nu mber EPA-HQ-OPP-2005-02 87 Pesticide Re-evaluati on Division Interim Registration R ev iew Decision



### •



### •

•

• the total acres treated wi th lactof en annually in the U.S. Wi th th e majority of RQ exceedances resulting from higher application rates for crops other than soybeans and peanuts , also considering the acifluorfen degradate RQ calculations mentioned above related t o chronic ri sk est imates, 99% oftota llac tofen use results in a small number of exposure scenario s with only slight excee dan ces of LOCs. Data suggest th at average application rate us ed by growers for soybeans is 0.12 lbs
. a.i./acre, wherea s the ecological ri s k assessment appropriately mod e led the maximum app licati o n rate of 0.2 lbs. a.i ./acre. Moreover , the average applic at io n rate used by growers f or peanu ts is 0. 17 lbs. a.i ./ acre, w here as th e eco logical ri sk assess ment appropriately modeled the maximum application rate of0.2lbs. a .i./ac re. Utilizing typical application rates results in re ductions of RQs to a certain degree, though LO Cs will sti ll be exceeded. Data s uggest that more than 98 percent of peanut acreage treated w ith Iactofen and more than 99 percent of soybean acreage treated with lactofen received one applicatio n per year. The ecolo gical risk asse ss ment appro priately modeled the maximum numb er of application s per year at two applicat ions. Howeve r, recogni zi ng that a more rea li sti c number of app li cations per y ea r of one would re s ult in a d ifferent ca lculation of RQ s, ultimately reducing the RQ s for a ll exposure scenar ios for birds and mammals. Data s ug gest th ere is little to no use of lactofen on severa l crops that we re identified as drivers in th e eco log ical ri sk assessment, such as Oregon strawberries and Florida f ruiting vegetables. Lactofen use on Florida fruiting vegetab le s is regis tered under F IFRA 24 (c) , Special Local Need (S LN). EPA proprietary data, w hich include u se of SLN products , s how no usage for Florida fruiting vegetables for 1 998-201 2 , suggest ing littl e or no lactofen use o n Florida fru itin g veg etables. Additionally, the state -specific use of strawberrie s was voluntarily canc e lled by the regis trant (70 FR 1 376), effective January 8, 20 14
. Levels of conc e rn are still exceeded for use sites with lower application rates and hi g h annuallactofen usage (e.g. soybeans), though the magnitude of those exceedances are lower. From a benefits standpoi nt , lactofen may be used as a tank-mix p artner w ith glyp hosate i n soybeans to man age several species of g lyphosate-res i stan t we ed s, such as kochia and common waterhemp. Additionally, in no-till soybean production, lactofen may be us e d as a burn-down treatment again st glypho sa te-resistant waterhemp. Lactofen a lso provid es a wider window of herbicide application than many other herbi cides and can be applied as a pr e -pl ant, pre- emergence or a postemergence treatment. That type of ap plicati o n flexibility is often very important to growers when factors outside their co ntro l , such as weather, direc t ly impacts their abili ty to compl ete their herbicid e treatments. With this use and u sage information , co mbined with several conservative elements of the risk assessment and the aforementioned uncertainties , the Agency does not b elie ve at this time that potential eco logical ri sks are of concern from the registered uses of lactofen.

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### 4. Endangered Spec ies Assessment Interim Regist rati on Review Deci sion

In November 2013, the EPA, along with the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheri es Service (NMFS) (collectively, the Services), and the U.S. Department of Agriculture (USDA) released a summary of th eirjoint Interim Approache s for assessing risks to listed species from pesticides. The Interim Approaches were developed jointly by the age ncies in response t o the Nat ional Academy of Sciences ' (NAS) re commendatio ns 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 r e port outlines recommendations on s pecific scientific and technical issues related to the development of pesticide risk assessments that EPA and th e Services must conduct in connection with their obligations under the Endangered Species Act (ESA) and FIFRA. T he joint Inte r im Approaches were released prior to a stakeholder workshop held on November 15 , 2013. In ad dition , the EPA presented the joint Interim Approaches at the December 2013 Pesticide Program Dialogue Com mittee (PPD C) and State-FIFRA Issues Research and Evaluation Group (SFIREG) meeting s, and held a stakeholder workshop in April 2014, allowing additional opportunitie s 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 Registrati o n Review decisions. The details of the joint Interim Approaches are co ntained in the wh ite paper " Interim Approaches for National-Level Pes ticide En dangered Species Act Assessments Based on the Recommendations oft he National Academy of Sciences Ap ril2013 Report ," dated November 1 , 2013. Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risk s of pesticides to listed species and their designated critical habitat, the ecological risk assessment supporting this Interim Registration Review Decision for lactof en does not contain a complete ESA analysis that includes effects determinations for specific listed species or designated critical habitat. Although EPA has not yet completed effects determinations for specific species or habitats, for this preliminary as ses sment EPA conducted a screening-le vel assessment for all taxa of non-target wildlife and plants that assumes for the sake of the assessment that listed species and designated critical habitats may be present in the vicinity of the application of lactofen. This screeni n g -level assess ment will allow EPA to focus its future evaluat ions on the types of species where the potential for effects exists once the scientific methods being developed by th e agencies have been fully ve tted. Once the agencies have fully developed and imp lemented the scientific methods necessary to complete ri sk assessments for endangered and threaten ed (listed) species and their designate d critical habitats, these method s wi ll be applied to subsequent analyses for lactofen as part of completing this registration review.



### 1 6Lactofe n Case 72 10 W\\ w.regulations.gov Docket Number EP A- HQ-OPP-2005-0287 Pe sticide Re

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### 5. Endocrine Disruptor Screening Program Interim Registrati on Review D ec ision

As required by FIFRA a nd FFDCA, EPA reviews numerous studies t o assess potential adverse outcomes from exposure to chemica l s. Co ll ectively , thes e s tudi es incl ude acute , s ubchronic and chron ic toxicity , including asse ss ment s of carci nogeni c ity, neuro toxicity, deve lopmen tal , repro ductive , and general or systemic toxicity. These stu die s include endpoints which may be susceptib le to endoc rine influence , including effects on end oc ri ne target organ histopat hology , org an weights, estrus cyclicity , sexual maturation, fe rtility, pregnancy rate s, reproductive loss , and sex ratios in offs p ring. For ecological hazard assessme n ts , EP A evaluates acute tests and chronic s tudi es that assess g rowth, developmental and reproductive effects in different taxonomic g roups. As part of its mo st recent registration deci s i o n for I acto fen, EPA reviewed thes e data and sele cted the most sensitive endpoints for relevant ri sk assessment scenarios from the ex i stin g hazard database. How ever, as requ ired by FFD CA sec tion 408(p) , l actofen is s ubject to th e endocrine screening part of the Endocrine Disrupter Screeni ng Program (EDSP)
. EPA has developed the ED S P to de termine whet h er certain substances (i ncluding pesticide active and other in gredie nts ) may have an effect in human s o r wild life si milar to an effec t produced by a " n atur ally occurr in g estrogen, o r other such endocr ine effec t s as the Administrator may designate." The EDSP emp loys a two- t iered approach to ma king the statutorily required determinations. Tier I consists of a battery of II sc re ening ass ays to identify the potential of a ch emi cal s ub stance to interact with th e estrogen , andro ge n , or thyroid (E, A , or T) hormo nal system s . Che micals that go throu g h T ier 1 screeni n g and are found to hav e the potential to interact withE , A, or T honnonal sys tem s will proceed to the next s tage of the EDSP where EPA will determine which , if any, of the Tier 2 tests are necessary based o n the available data. Tier 2 testin g i s designed to identify any ad verse endocrine

- related effects caused b y the substance , and establish a dose-response rel at ions hip between the dose and theE , A , or T effect. Under FFD CA sec tion 408(p) , the Agency must sc reen all p esticide chemicals. Between October 2009 and February 2010, EPA issued te st orders/data call-in s for the fir s t group of 67 chemicals, which contains 58 pesticide active in g redients and 9 inert in gredient s. A second list of chemica ls identified for EDS P screenin g was publi s hed on June 14 , 20 1 3 1 and includes some pesticides sc hedul ed fo r Registratio n Review and chemicals found in water. Neither of these li s ts should be cons tru ed as a list of known o r likely endoc rine disrupters. For further information on the s tatus of the EDSP, the policie s a nd procedures , the lists of chemicals, future li sts , the test guideli n es and the Tier I screening battery , ple ase vi sit our website. 2 Lactofen is on List 2
. Li st 2 re p resents th e next set of chemicals for which EPA in tends to i ss ue test orders/data call-ins in the near fut ure. In the interim , EPA is making no human health or environmental safety findings associated w ith the EDSP sc r eenin g of lactofen. Befor e comp leting t his registratio n review, the Agency will make an EDSP FFD C A sect ion 408(p) determination.

1 See http: //www.regulations. gov/ # !documentDet ail;D=EPA-HQ-OPPT -2009

- 0 4 77-0074 for the fin a l s econd l i st of chem icals. 2 http://www.epa.gov/endo/

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### IV
. INTERIM REGISTRATION REVIEW DECISION In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Interim Registration Review Decision. Except for the EDSP and ESA components of this case , the Agency has made the following Interim Re g i stration Review Deci sion: (I) considering all lines of evidence regarding the risk characterization of lactofen exposure , including potential chronic risk e x posure likely to come from acifluorfen rather than the parent lactofen , th e use and u s age information , and benefit analysis, the Agency does not believe at this time that potential ecological risks are of concern from the registered uses of lactofen; (2) potential human health ri sks due to lactofen exposure are below the Agency 's LOCs ; (3) the Agency intends to require additional data , a non-guideline foliar dissipation s tudy, to help determin e an accurate half

- life for lactofen, and provide more represen tativ e ri s k estimates; and (4) chang es to the affected re gistrations and th e ir labeling are not needed at th is time. In this interim registration review decision , E P A is making no hum an health or environmental safety findi ngs a ssoc iated wi th the E D SP sc reening of !actofe n , nor is it making a compl ete endangered s pecies finding. The Agency 's final registration review decision for l ac to fen will depen d u pon both the result of an ESA Sec ti o n 7 consultation with the Services, and an EDSP FFDCA sect io n 408(p) determin at ion. 

### V. NEXT STEPS AND TIMELINE A
. Implementation of Mitigation Measures and Requirement of New Data As sta ted in Sectio n IV , no mitigation measures are

**equi d**  for !acto f en at this time
. However, a data call-i n will be issued to require s ubmission of a non-guideli ne foliar dissipation s tud y. 

### B. Final R egistration Review Decision EPA will make a final registration review decision for l actofen after E SA Section 

### 7 co n s ultation with the Serv ice s occurs and an EDSP FFDCA section 408(p) determination has been made.

18