Lactofen Case 7210 

"'' w.r..:gulations.gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Interim Registration Review Decision 

Lactofen 

Interim Registration Review Decision 

Case Number 7210 

Approved by: 

Date: 

December 2014 

G C-hcy..pl P ~ ,'J-) 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 
Lactofen Case 7210 

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Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Table of Contents 

Interim Registration Review Decision 

I. Introduction .................................................................................................... .......... ] 

II. Use an d Usage .......................................................................................................... 4 

III. Scientific Assessments ............................................................................................. 4 

IV. Interim Registration Review Decision ............. .... ... ........................................ ....... 15 

V. Next Steps and Timeline .............................................................. .......................... 15 

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Docket Number EPA-HQ-OPP-2005-0287 

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I. INTRODUCTION 

Interim Registration Review Decision 

This document is the Environmental Protection Agency's (EPA or the Agency) Interim 

Registration Review Decision for lactofen (PC code 128888) and is being issued pursuant to 40 

CFR sections 155.56 and 155.58. A registration review decision is the Agency's determination 

whether a pesticide meets, or does not meet, the standard for registration in the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA). The Agency may issue, when it 

determines it to be appropriate, an interim registration review decision before completing a 

registration review. Among other things, the interim registration review decision may: 1) require 

new risk mitigation measures; 2) impose interim risk mitigation measures; 3) identify data or 

information required to complete the review; and 4) include schedules for submitting the 

required data, conducting the new risk assessment and completing the registration review. For 

further information on lac to fen, additional documents can be found in EPA's .public docket 

(EPA-H Q-0 PP-2005-0287) at www .regulations. gov. 

FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the 

continuous review of existing pesticides. All pesticides distributed or sold in the United States 

generally must be registered by the EPA based on scientific data showing that they will not cause 

unreasonable risks to human health or to the environment when used as directed on product 

labeling. The registration review program is intended to make sure that, as the ability to assess 

and reduce risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the registration review 

program, the Agency periodically re-evaluates pesticides to make sure that as these changes 

occur, products in the marketplace can continue to be used safely. Information on this program 

is provided as www.epa.gov/oppsnd I /registration review/. 

In 2006, the Agency implemented the registration review program pursuant to FIFRA 

section 3(g) and will review each registered pesticide every 15 years to determine whether it 

continues to meet the FIFRA standard for registration. 

Lactofen was first registered in 1987, and therefore was not subject to reregistration 

because it was registered after November 1984. 

Pursuant to 40 CFR § 155.50, the Agency formally initiated registration review for 

lactofen (case 721 0). The following bullets highlight significant events that have occurred 

during the registration review of lactofen and can be found in public docket (EPA-HQ-OPP2005-0287, accessed at www.regulations.gov): 

• February 2, 2007 - Publication of the Lacto.fen Summary Document for a 60-day public 

comment period. The Summary Document included the Preliminary Work 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. 

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

• March 20, 2013 - The Agency published the Preliminary Environmental Fate and 

Ecological Risk Assessment in Support of the Registration Review of Lactofen and the 

Lactofen- Occupational Exposure/Risk Assessment for Lactofen Use on Soybean, Snap 

Bean, Strawberry (Non-Bearing), and Conifer Seedlings for a 60-day public comment 

period. No comments were received during the comment period. 

• July 23, 2014- The Agency published the Lactofen Proposed Interim Registration 

Review Decision for a 60-day public comment period. The Agency received two 

comments; one from the Center for Biological Diversity, and one from the registrant, 

Valent Corporation. 

• December 2014 -The Agency is now publishing the Lac to fen Interim Registration 

Review Decision. This document, and those found above and after can be found in 

docket number EPA-HQ-OPP-2005-0287 at www.regulations.gov. 

Public Comments 

During the 60-day public comment period on the Lactofen Proposed Interim 

Registration Review Decision, 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). 

Valent's comment addressed the methodology and endpoints used in drafting the ecological 

preliminary risk assessment. Neither comment resulted in a change in the proposed interim 

decision for lactofen. 

The Agency 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 submitted by the Center for Biological Diversity in EPA-HQ-OPP-2005-0287-

0027. 

Comment: The Center for Biological Diversity's (CBD) comments focus on the EPA's 

independent duty under the Endangered Species Act (ESA) to consult with the U.S. Fish 

and Wildlife Service and the National Marine Fisheries Service (the Services) on the 

registration review of /acto fen. 

Agency Response: EPA has reviewed the comments from CBD on the registration review 

docket opening for lactofen and plans to address many of the concerns raised by CBD as part 

of the implementation plan for assessing the risks of pesticides to listed 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 registration 

review decision for lactofen. 

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Docket Number EPA-HQ-OPP-2005-0287 

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Interim Registration Review Decision 

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 for 

assessing risks to listed species from pesticides. The Interim Approaches were 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. TheN AS 

repo1t outlines recommendations on specific scientific and technical issues related to the 

development of pesticide risk assessments that EPA and the Services must conduct in 

connection with their obligations under the Endangered Species Act (ESA) and FIFRA. 

The joint Interim Approaches were released prior to a stakeholder workshop held on 

November 15, 2013. In addition, the EPA presented the joint Interim Approaches at the 

December 2013 Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues 

Research and Evaluation Group (SFIREG) meetings, and held a stakeholder workshop in 

April 2014, 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 joint 

Interim Approaches are contained in the white paper "Interim Approaches for National-Level 

Pesticide Endangered Species Act Assessments Based on the 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 implementation of the 

Interim Approaches to assess the potential risks of pesticides to listed species and their 

designated critical habitat, the ecological risk assessment supporting this Interim Registration 

Review Decision for lactofen 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 

assessment EPA conducted a screening-level 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 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 methods being developed by the agencies 

have been fully vetted. While the agencies continue to develop a common method for ESA 

analysis, the regulatory section of the Interim Registration Review Decision document will 

describe the level of ESA analysis completed for this particular registration review case. 

Once the agencies have fully developed and implemented the scientific methods necessary to 

complete risk assessments for endangered and threatened (listed) species and their designated 

critical habitats, these methods will be applied to subsequent analyses for lactofen as part of 

completing this registration review. 

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Pesticide Re-evaluation Division 

Interim Registration Review Decision 

Comment submitted by Valent Corporation in EPA-lJQ-OPP-2005-0287-0028. 

Comment: Valent 's comments focus on the EPA's ecological preliminary risk assessment 

entitled "Preliminary Environmental Fate and Ecological Risk Assessment in Support of 

the Registration Review of Lactofen ", dated March 13, 2013, which can be found in the 

public docket in EPA-HQ-OPP-2005-0287-021. Valent makes numerous comments 

critiquing the Agency's risk assessment models and procedures, as well as several other 

specific comments pertaining to endpoint selection and the potential risk .findings spec!fic 

to lactofen identified in the risk assessment. 

Agency Response: The Agency thanks Valent for its comments. EPA notes that the 

exposure assessment methods, tools, and assumptions used in the preliminary risk 

assessments have evolved over time and have been well documented and peer reviewed. 

Where appropriate, the Agency will consider Valent's general methodological comments 

as noted. For more detailed and specific responses to Valent's comments, please refer to 

the document entitled, "Response to Comments Regarding the Lactofen Registration 

Review Preliminary Risk Assessment That Were Submitted During Registration Review 

Proposed Interim Decision Public Comment Period', dated December 2, 2014, which can 

be found in the public docket at www.regulations.gov. 

II. USE AND USAGE 

Lactofen is a light dependent peroxidizing herbicide (LDPH). LDPHs are a class of weed 

control chemicals that act in plants by inhibiting the enzyme protoporphyrinogen oxidase 

(protox), which is the last common enzyme in the heme and chlorophyll biosynthetic pathways. 

Protox exists in both plants and animals, and the enzyme from both sources has been shown to be 

sensitive to many LDPHs. 

Lactofen is registered for use on soybean, cotton, peanuts, conifer seedlings, and kenaf. 

It also has state-specific (Florida) uses, registered under FIFRA section 24 (c), on snap beans, 

fruiting vegetables, and okra. Soybeans and peanuts are the dominant use patterns for lactofen, 

representing approximately 99% of the total estimated acres treated annually with lactofen in the 

U.S. Data indicate that the largest use of lactofen is on soybeans; both in terms 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 information on the use and usage of lactofen, see Use/ Usage 

Refinement in Support of Registration Review of Lactofen (128888), dated April 15,2014, in the 

public docket (EPA-HQ-OPP-2005-0287) which can be accessed 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 human health risk assessment, see Lactofen -

Occupational Exposure/Risk Assessment for Lactofen Use on Soybean, Snap Bean, Strawberry 

(Non-Bearing), and Conifer Seedlings, dated July 16, 2012; Lactofen Summary Document, dated 

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Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

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 public docket (EPA-HQ-OPP-2005-0287) 

which can be accessed on http://www.regulations.gov/. 

1. Summary Of Risk Estimates 

Dietary Exposure 

As indicated in the Lactofen Summary Document, the Agency determined that previously 

completed 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 

As stated above, there are no residential uses for lactofen, so an aggregate assessment 

would only include food and drinking water exposures. As previously mentioned, the Agency 

has determined there are no dietary risks that exceed the Agency's LOC, with all exposures less 

than 1% of the aPAD and cPAD. 

In the Lactofen: Human Health Risk Assessment for Proposed Uses on Fruiting 

Vegetables and Okra document, dated January 8, 2007, the Agency also conducted aggregate 

risk assessments for acifl uorfen, which is an environmental de gradate of two registered 

herbicides, lactofen and sodium acifluorfen. Therefore, an aggregate assessment was required 

for acifluorfen considering exposures from both active ingredients. The assessment included 

food exposure from tolerance level residues from sodium acifluorfen applications, residential 

handler exposure from spot treatments of sodium acifluorfen, and drinking water exposure to 

acifluorfen as a result of environmental degradation of lac to fen. The aggregate assessments for 

all exposure durations were below the Agency's level of concern, with the acifluorfen exposures 

at 6% of the aPAD. Short-term aggregate risk was not a concern, with a margin of exposure 

(MOE) equal to 16,000, which exceeds the targets MOE of I ,000. Long-term aggregate risk for 

acifluorfen was also not a concern, with the most highly exposed subgroup (infants Jess than one 

year old) at 37% of the cPAD. 

Cumulative Effects 

Section 408(b)(2)(D)(v) of the Federal Food, Drug, and Cosmetic Act (FFDCA) requires 

the Agency to consider the cumulative effects of exposure to lactofen and other substances that 

have a common mechanism of toxicity. These considerations include the possible cumulative 

effects of such residues on infants and children. 

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• 

Lactofen is a member of the diphenyl ether group of herbicides, as are sodium acifluorfen 

and oxyfluorfen. However, EPA has not made a common mechanism of toxicity finding for 

lactofen or these other substances. 

Occupational Exposure 

As indicated in the Lactofen - Occupational Exposure/Risk Assessment for Lactofen Use 

on Soybean, Snap Bean, Strcnvberry (Non-Bearing), and Conifer 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 application. However, none of the occupational handler exposure scenarios 

resulted in combined dermal and inhalation risks of concern (MOEs less than 300), with either 

baseline attire, with the addition of chemical-resistant gloves, and/or engineering controls, such 

as enclosed cockpits and closed 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 lactofen following use on soybeans and conifer seedlings 

when those workers re-enter previously treated areas. However, there were no risks of concern 

associated with these post-application handler exposure scenarios (MOEs range 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 reviewed the 

poisoning incident data on lactofen in 2006, in the following databases: OPP Incident Data 

Systems (IDS), Poison Control Centers, California Department of Pesticide Regulation, National 

Pesticide Information Center (NPIC), and National Institute of Occupational Safety and Health's 

Sentinel Event Notification System for Occupational Risks (NIOSH SENSOR). There were few 

reports 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 tolerances are listed under 40 CFR 180.43 for lactofen. 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,.listed fish, 

estuarine/marine invertebrates, aquatic non-vascular plants, mammals, birds, reptiles, terrestrialphase amphibians, and terrestrial plants (dicots). These risks are summarized below. For 

detailed discussions of all aspects of the environmental risk assessment, see the Preliminaty 

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Pesticide Re-evaluation Division 

Interim Registration Review Decision 

Environmental Fare and Ecological Risk 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 (listed) species 

assessment for lactofen and identified potential risks to fish, estuarine/marine invertebrates, 

aquatic non-vascular plants, mammals, birds, reptiles, terrestrial-phase amphibians, and 

terrestrial non-target plants, particularly dicots. The Agency is currently working 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-level risks to listed species will be enumerated 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 aerobic soil 

metabolism and hydrolysis. Lactofen is not persistent (half-life less 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 

be transported off site primarily through spray drift and also through erosion; however, lactofen 

is likely to degrade before the eroded soil particles runoff from the application site. 

Lactofen is expected to readily degrade in both terrestrial and aquatic environments under 

aerobic and anaerobic conditions, and is considered slightly to hardly mobile, and nonvolatile. 

Lactofen is not persistent in soil, with half-lives ranging from 1 to 3 days in aerobic soil 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 rapid degradation. Due to a lack of data, a 35-day default foliar dissipation halflife was used. 

The environmental de gradate of lactofen that is considered to be of exposure concern is 

acifluorfen, which is also registered as a unique pesticide active ingredient (PC code 114402). 

This degradate formed at increasing concentrations through the environmental fate studies, and 

was still present at study termination. This 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 estimates were made due to acifluorfen's high persistence and mobility 

relative to lactofen. 

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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 (surrogate for Aquatic-Phase Amphibians) and 

Estuarine/ Marine Fish 

Risk Quotients (RQs) for freshwater fish (surrogate 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-listed (0.5) species 

LOCs. Therefore, risk to freshwater and estuarine/marine fish is not expected on an acute 

exposure basis. 

However, as stated 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 shown to be highly sensitive to many LDPHs. Several studies have 

documented enhanced toxicity of LDPHs to fish 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 have been raised that 

guideline chronic exposure laboratory tests may underestimate the toxicity of LDPH in the 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 factor 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 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. Chronic exposure RQs for fish were calculated with and without the 29X adjustment 

factor. RQs for fish that may not receive 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 LOC (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 listed estuarine/marine invertebrates (0.05) is exceeded (RQ=0.096). 

There are no chronic data for freshwater invertebrates, but the estuarine/marine acute 

endpoint is two orders of magnitude lower than the freshwater acute endpoint. While an acuteto-chronic ratio (ACR) can be applied, it would result in RQs orders of magnitude lower than the 

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estuarine/marine endpoint. Based on the estuarine/marine acute endpoint, there are no chronic 

LOC (I) exceedances for aquatic invertebrates, as the highest RQ is 0.12. At this time, the 

Agency is not applying the 29X factor to aquatic invertebrates, and therefore the risk assessment 

does not indicate a potential for chronic risk to aquatic invertebrates. 

Effects to Aquatic Plants 

RQs for non-listed aquatic vascular plants ranged from 0.03 to 0.07, RQs for listed 

aquatic vascular plants ranged 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. 

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 lactofen. 

Risk to Terrestrial Organisms 

Effects to Mammals 

Acute RQs were not calculated for mammals because only non-definitive acute oral 

toxicity data were available. Based on the available acute toxicity data, no mortality was 

observed in any of the mammalian studies conducted on lactofen technical or its formulated 

products at the highest concentrations/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 ( I) for chronic dose-based exposure for mammals of all size classes for all use patterns 

(RQs range from 0.42 to 37.48). Additionally, there are exceedances of the chronic LOC (1) for 

chronic dietary-based exposure (RQs range from 0.11 to 4.32). 

There are no acute exceedances for mammals based on the degradate acifluorfen 

exposure, as all RQs 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 

fruiting vegetables), the LOC (I) is exceeded (RQs range from 1.07 to 2.34). The conifer 

seedling use also exceeds the LOC (1) for small mammals consuming short grass (RQ is 1.14). 

F;f(ects to Birds, Reptiles, and Terrestrial-Phase Amphibians 

Acute RQs were not calculated for birds, reptiles, and terrestrial-phase amphibians 

because only non-definitive acute and sub-acute toxicity endpoints were available. 

Based on the currently labeled maximum application rates, there is chronic dietary-based 

exposure exceedanc.e of the LOC (RQ=I.61 for the Florida fruiting vegetable and okra use 

pattern). No other use pattern has an RQ>0.79. However, the acifluorfen degradate exhibits 

greater toxicity to birds than the parent, lactofen. There were exceedances of the chronic LOC 

(1) for all use patterns for birds feeding on short grass (RQs ranged from 1.20 to 3.07). RQs also 

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Interim Registration Review Decision 

exceeded the LOC (I) for two uses (Florida fruiting vegetables and okra and Oregon 

strawberries) 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 Terrestrial Invertebrates 

Both lactofen and acifluorfen are classified as practically non-toxic to honeybees on an 

acute exposure basis. Only non-definitive endpoints are available and RQs were not caiculated. 

Based on the low toxicity of lactofen on honeybees, 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, risk to non-target plants is indicated. Based on the 

available data, monocots are less sensitive to lactofen than dicots, and generally vegetative vigor 

is a more sensitive life-stage than seedling emergence. For both aerial and ground applications 

the LOC ( I) for both listed and non-listed plants is exceeded for 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 

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) (RQs ranged from I.06 to 2.17). RQs based on spray drift alone exceed the 

LOC (1) for dicots for all rates for both aerial (RQs ranged from 5.56 to 46.55) and ground (RQs 

ranged from 1.11 to 9.31) applications. RQs for monocots for drift alone do not exceed the LOC 

(I) (RQs range from <O.I to 0.58). 

3. Ecological Incidents 

A review of the Ecological Incident Information System (EllS) database for incidents 

involving lactofen and the acifluorfen degradate was conducted on January 25, 20 I2. Four 

incidents for lactofen are reported in the database. Of these, three are plant incidents that 

occurred from use on agricultural areas. The fourth incident involved mortality 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 ingredient) on beans (likely 

soybeans). This incident also reported mortality to an unknown number of unspecified fish 

species, and was also deemed to be unlikely. 

Similarly, a search of the Avian Incident Monitoring System (AIMS; 

http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfin) was conducted on 

January 25, 2012. AIMS is a database administered by the American Bird Conservancy that 

contains publicly available data on reported avian incidents involving pesticides. No incidents 

involving lactofen or acifluorfen were found. 

Pesticide registrants report certain types of incidents to the Agency as aggregate counts of 

incidents occurring per product per quarter. One aggregated plant incident has been reported to 

the Agency associated with lactofen, in the summer of2000. Unless further information 

regarding this aggregate incident is discovered, it will be assumed that it resulted from registered 

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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 Characterization 

1. Human 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 of human health 

risks is necessary. 

2. Ecological Risk 

EPA has determined that there is potential for adverse effects to non-listed fish (and 

aquatic-phase amphibians), estuarine/marine invertebrates, aquatic non-vascular plants, 

mammals, birds, reptiles, terrestrial-phase amphibians, and terrestrial plants (dicots). 

Considerations Regarding Estimated Ecological Risk 

Although the Agency has determined that there are potential risks to certain taxa, there 

are areas of uncertainty in regards to the Agency's calculation of risk oflactofen to the affected 

taxa. These uncertainties include: 

• For chronic risk to mammals, a 35-day default foliar dissipation half-life was used to 

calculate RQs. In some fate studies, lactofen is shown to degrade much more 

quickly. To address this uncertainty, RQs were modeled using a hypothetical three 

day half-life. Use of a three day half-life results in a 40% reduction in the RQs (e.g., 

14.64 to 8.66). Using a verified half-life would likely result in reduced RQs for 

mammals. Therefore, the Agency intends to require a non-guideline foliar dissipation 

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 lactofen on Florida 

fruiting vegetables. Additionally, the strawberry use has been voluntarily cancelled 

by the registrant (70 FR 1376), effective January 8, 2014. When removing these 

rates, the next highest maximum rate, for conifer seedlings, results in RQs less than 

half of those estimated from the Florida fruiting vegetable use (e.g., 18.30), but still in 

exceedance of the LOC. 

• Given that lactofen degrades quickly (one to three days) in the environment via 

aerobic soil 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, small mammals eating 

short grass, for the conifer seedlings use (RQ = 1.14 ). 

For more information on available use and usage data, please see the Use and Usage 

Information section below. 

For chronic risk to freshwater and estuarine/marine fish, the 29X interim adjustment 

factor due to lactofen being an LDPH causes the RQs 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 conditions might mitigate the 

effect. It would seem reasonable to assume that fish inhabiting shallow, clear water 

bodies 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 u V-enhanced 

toxicity. At higher latitudes, the sun is lower in the sky, so uV light must travel a 

greater distance through ozone-rich portions of the atmosphere, and therefore expose 

those latitudes to less u V radiation. Alternately, u V intensity decreases with lower 

elevation because there is more atmosphere to absorb u V rays. The Agency also · 

realizes many other factors can impact the amount of u V light, such as time of day, 

time of year, stratospheri c ozone and weather (cloud cover). Therefore, chronic RQ 

estimates for freshwater and estuarine/marine fish associated with the interim 

adjustment factor are uncertain. 

3. Other Considerations 

Although there are estimated risks which exceed the LOC for certain taxa, the Agency 

considers multiple lines of evidence when making a risk management decision. EPA has taken 

into account data on lactofen-specific use patterns that provide a more accurate picture of 

lactofen use in the field. Additionally, data are available on the benefits of using Jactofen in 

different crop systems to meet certain needs. Please see below for more details. 

Use and Usage Information 

There are several factors from available use and usage information that have been 

gathered and outlined below. For more information on the use and usage information, please see 

Use/ Usage Refinement in Support of Registration Review of Lactofen (128888), dated April 15, 

2014. 

• Data suggest that the actual acreage of crops in the United States treated with lactofen 

is very minimal. The use and usage report indicates that less than 1% of soybean 

acreage is treated with lactofen. This I% (approximately 1 million acres) represents 

95% of the total acres treated with 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 total lactofen treated acres in 

the U.S. Therefore, soybean and peanuts together represent approximately 99% of 

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• 

• 

• 

• 

the total acres treated with lactofen annually in the U.S. With the 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 to chronic risk estimates, 99% oftotallactofen use results in a small number 

of exposure scenarios with only slight exceedances of LOCs. 

Data suggest that average application rate used by growers for soybeans is 0.12 lbs . 

a.i./acre, whereas the ecological risk assessment appropriately modeled 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 

appropriately modeled the maximum application rate of0.2lbs. a.i./acre. Utilizing 

typical application rates results in reductions of RQs to a certain degree, though LOCs 

will still be exceeded. 

Data suggest that more than 98 percent of peanut acreage treated with I acto fen and 

more than 99 percent of soybean acreage treated with lactofen received one 

application per year. The ecological risk assessment appropriately modeled the 

maximum number of applications per year at two applications. However, recognizing 

that a more realistic number of applications per year of one would result in a different 

calculation of RQs, ultimately reducing the RQs for all exposure scenarios for birds 

and mammals. 

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 strawberries and Florida 

fruiting vegetables. Lactofen use on Florida fruiting vegetables is registered under 

FIFRA 24 (c), Special Local Need (SLN). EPA proprietary data, which include use 

of SLN products, show no usage for Florida fruiting vegetables for 1998-201 2, 

suggesting little or no lactofen use on Florida fruiting vegetables. Additionally, the 

state-specific use of strawberries was voluntarily cancelled by the registrant (70 FR 

1376), effective January 8, 2014. Levels of concern are still exceeded for use sites 

with lower application rates and high annuallactofen usage (e.g. soybeans), though 

the magnitude of those exceedances are lower. 

From a benefits standpoint, lactofen may be used as a tank-mix partner with 

glyphosate in soybeans to manage several species of glyphosate-resistant weeds, such 

as kochia and common waterhemp. Additionally, in no-till soybean production, 

lactofen may be used as a burn-down treatment against glyphosate-resistant 

waterhemp. Lactofen also provides a wider window of herbicide application than 

many other herbicides and can be applied as a pre-plant, pre-emergence or a postemergence treatment. That type of application flexibility is often very important to 

growers when factors outside their control, such as weather, directly impacts their 

ability to complete their herbicide treatments. 

With this use and usage information, combined with several conservative elements of the 

risk assessment and the aforementioned uncertainties, the Agency does not believe at this time 

that potential ecological risks are of concern from the registered uses of lactofen. 

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4. Endangered Species Assessment 

Interim Registration Review Decision 

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 for assessing risks 

to listed species from pesticides. The Interim Approaches were 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 report outlines recommendations on 

specific scientific and technical issues related to the development of pesticide risk assessments 

that EPA and the Services must conduct in connection with their obligations under the 

Endangered Species Act (ESA) and FIFRA. 

The joint Interim Approaches were released prior to a stakeholder workshop held on 

November 15, 2013. In addition, the EPA presented the joint Interim Approaches at the 

December 2013 Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues 

Research and Evaluation Group (SFIREG) meetings, and held a stakeholder workshop in April 

2014, 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 joint Interim Approaches are 

contained in the white paper " Interim Approaches for National-Level Pesticide Endangered 

Species Act Assessments Based on the Recommendations ofthe National Academy of Sciences 

April2013 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 risks of pesticides to listed species and their 

designated critical habitat, the ecological risk assessment supporting this Interim Registration 

Review Decision for lactofen 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 

assessment EPA conducted a screening-level 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 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 methods being developed by the agencies have 

been fully vetted. Once the agencies have fully developed and implemented the scientific 

methods necessary to complete risk assessments for endangered and threatened (listed) species 

and their designated critical habitats, these methods will be applied to subsequent analyses for 

lactofen as part of completing this registration review. 

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5. Endocrine Disruptor Screening Program 

Interim Registration Review Decision 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chron ic toxicity, including assessments of carcinogeni city, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates 

acute tests and chronic studies that assess growth, developmental and reproductive effects in 

different taxonomic groups. As part of its most recent registration decision for I acto fen, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

lactofen is subject to the endocrine screening part of the Endocrine Disrupter Screening Program 

(EDSP). 

EPA has developed the EDSP to determine whether certain substances (including 

pesticide active and other ingredients) may have an effect in humans or wildlife similar to an 

effect produced by a "naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate." The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier I consists of a battery of II screening assays to identify 

the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or 

T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the 

potential to interact withE, A, or T honnonal systems will proceed to the next stage of the EDSP 

where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available 

data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the 

substance, and establish a dose-response relationship between the dose and theE, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20 131 and includes some 

pesticides scheduled for Registration Review and chemicals found in water. Neither of these 

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 guidelines and the Tier I screening battery, please visit our website.2 

Lactofen is on List 2. List 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 safety findings associated with the EDSP screening of lactofen. Before 

completing this registration review, the Agency will make an EDSP FFDCA section 408(p) 

determination. 

1 See http: //www.regulations. gov/# !documentDetail;D=EPA-HQ-OPPT-2009 - 04 77-0074 

for the fina l s econd l i st of chemicals. 

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 Registration Review Decision: (I) considering all 

lines of evidence regarding the risk characterization of lactofen exposure, including potential 

chronic risk exposure likely to come from acifluorfen rather than the parent lactofen, the use and 

usage 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 

risks due to lactofen exposure are below the Agency's LOCs; (3) the Agency intends to require 

additional data, a non-guideline foliar dissipation study, to help determine an accurate half-life 

for lactofen, and provide more representative risk estimates; and ( 4) changes to the affected 

registrations and their labeling are not needed at this time. 

In this interim registration review decision, EPA is making no human health or 

environmental safety findings associated with the EDSP screening of !acto fen, nor is it making a 

complete endangered species finding. The Agency's final registration review decision for 

lac to fen will depend upon both the result of an ESA Section 7 consultation with the Services, 

and an EDSP FFDCA section 408(p) determination. 

V. NEXT STEPS AND TIMELINE 

A. Implementation of Mitigation Measures and Requirement of New Data 

As stated in Section IV, no mitigation measures are equi d for !acto fen at this time. 

However, a data call-in will be issued to require submission of a non-guideline foliar dissipation 

study. 

B. Final Registration Review Decision 

EPA will make a final registration review decision for lactofen after ESA Section 7 

consultation with the Services occurs and an EDSP FFDCA section 408(p) determination has 

been made. 

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