Lactofen Case 7210 

www.regulations.gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Lactofen 

Proposed Interim Registration Review Decision 

Proposed Interim Registration Review Decision 

Case Number 7210 

July 2014 

Approved by: \!'-S? 

~ 

~ --Q.s--

Director 

Pesticide Re-evaluation Division 

Date: ~\\ zcN\ 
Lactofen Case 7210 

www.regulations.gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Table of Contents 

Proposed Interim Registration Review Decision 

I. Introduction ........................................... ........... ............................ .... ........................ ) 

II. Use and Usage ........ .... .... .... .................................................................... .... .... ....... ... 4 

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

TV . Proposed Interim Registration Review Decision ................................................... 15 

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

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Lactofen Case 72 10 

www.regulations.gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

I. INTRODUCTION 

Proposed Interim Registration Review Decision 

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

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-HQ-OPP-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/oopsndllregistration 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. 

Lac to fen 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 7210). The following highlights significant events that have occurred during the 

registration review of lactofen and can be found in public docket (EPA-HQ-OPP-2005-0287, 

accessed at www.regulations.gov): 

• February 2, 2007 - Publication of the Lactofen 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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Docket Number EPA-1-JQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Proposed Interim Registration Review Decision 

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

• March 20, 20 I 3 - 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 Lac to fen 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 2014 - The Agency is now publishing the Lactofen Proposed Interim Registration 

Review Decision, in docket number EPA-HQ-OPP-2005-0287 for a 60-day public 

comment period. 

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 LD PHs. 

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

It also has state-speci fie (Florida) uses 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 (1 28888), dated April 15, 2014, in the public docket (EPA-HQ-OPP-2005-0287) which 

can be accessed on http://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 

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/. 

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Lactofcn Case 721 0 

www.regulations.gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

1. Summary Of Risk Estimates 

Dietary Exposure 

Proposed Interim Registration Review Decision 

As indicated in the Lactofen Summa!y Document, the Agency determined that previously 

completed dietary assessments for lactofen are adequate 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 1% ofthe acute and chronic population adjusted dose (aPAD and cPAD). 

Residential Exposure 

There are no residential uses for lactofen. Therefore, the Agency determined a residential 

assessment was not necessary. 

Aggregate Exposures 

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

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

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

than 1% ofthe aPAD and cPAD. 

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

Vegetables and Okra document, the Agency also conducted aggregate risk assessments for 

acifluorfen, which is an environmental 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 lactofen. The aggregate assessments for all exposure durations 

were below the Agency's level of concern, with the acifluorfen assessments at 6% ofthe aPAD. 

Short-term aggregate risk was not a concern, with a margin of exposure (MOE) equal to 16,000, 

which exceeds the targets MOE of 1 ,000. Long-term aggregate risk for acifluorfen was also not 

a concern, with the most highly exposed subgroup (infants less 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. 

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 oftoxicity finding for 

lactofen for these compounds and other substances. 

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Lactofen Case 72 10 

www.regulations.gov 

Docket umber EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Occupational Exposure 

Proposed Interim Registration Review Decision 

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

on Soybean, Snap Bean, Strawberry (Non-Bearing), and Conifer Seedlings document, the 

Agency has determined that there is a potential for short- and intermediate-term dermal and 

inhalation occupational exposure to lactofen during handling activities, such as mixing, loading, 

and application. However, none of the occupational handler exposure scenarios that were 

assessed resulted in combined dermal and inhalation risks of concern (MOEs Jess 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 Jactofen 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). 

2. Human Incidents 

As indicated in the Lactofen: Human Health Risk Assessment for Proposed Uses on 

Fruiting Vegetables and Okra document, in 2006, the Agency reviewed the poisoning incident 

data on lactofen 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 (and aquaticphase amphibians), estuarine/marine invertebrates, aquatic non-vascular plants, mammals, birds, 

reptiles, terrestrial-phase amphibians, and terrestrial plants (dicots). These risks are summarized 

below. For detailed discussions of all aspects of the environmental risk assessment, see the 

Preliminary Environmental Fate and Ecological Risk Assessment in Support of the Registration 

Review ofLactofen, published on March 20, 2013 in the public docket (EPA-HQ-OPP-2005-

0287) which can be accessed on http://www.regulations.gov/. 

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Lactofen Case 721 0 

www.r<;:gu lations.gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Proposed Interim Registration Review Decision 

The Agency also completed a screening-level endangered and threatened (listed) species 

assessment for lactofen and identified potential risks to fish (and aquatic-phase amphibians), 

estuarine/marine invertebrates, aquatic non-vascular plants, mammals, birds, reptiles, terrestrialphase 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 is 

transported off site primarily through spray drift but 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. 

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

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

This degradate fonned 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 acitluorfen exposure due to lactofen use are estimated 

separately. These estimates were made due to acitluorfen's high persistence and mobility 

relative to lactofen. 

Terrestrial animal exposure estimates are based on the residue levels of lactofen and 

acitluorfen. The formation of acitluorfen 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. 

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Lactofen Case 7210 

www.reg,ulations.gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Proposed Interim Registration Review Decision 

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 <0.012 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 adjust 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 u V light 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 7.12, 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, with an RQ 

as high as 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 

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

LOC (1) exceedances for aquatic invertebrates, as the highest RQ is 0.12. At this 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. 

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Lactofen Case 7210 

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Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Effects to Aquatic Plants 

Proposed Interim Registration Review Decision 

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

aquatic vascular 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-listed 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 lvfammals 

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 ( 1) 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 (1) 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). 

Effects 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 exceedance of the LOC (RQ=1.61 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, lac to fen. There were exceedances of the chronic LOC 

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

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

strawberries) for tall grass (RQs were 1.41 and 1.05, respectively) and broadleaf plants/small 

insects (RQs were 1. 73 and 1.28, respectively). 

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Lac to fen Case 7210 

www.regulations.gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Proposed Interim Registration Review Decision 

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 calculated. 

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 (1) 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 

1 0.45). Monocots inhabiting semi-aquatic areas result in exceedances at higher rates (0.25, 0.38, 

and 0.512 lbs ai/ A) (RQs ranged from 1.06 to 2.17). RQs based on spray drift alone exceed the 

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

ranged from 1.11 to 9.3 1) applications. RQs for monocots for drift alone do not exceed the LOC 

(1) (RQs range from <0.1 to 0.58). 

3. Ecological Incidents 

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

involving lactofen and the acifluorfen de gradate was conducted on January 25, 2012. Four 

incidents for lactofen are reported in the database. Of these, three are 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/abcprograrns/policy/toxins/airns/aims/index.cfm) 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 of 2000. Unless further information 

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

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. 

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Lactofen Case 7210 

www. regulations. gov 

Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Proposed Interim Registration Review Decision 

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). 

Uncertainties Regarding 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 of lac to fen 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 &.66). Therefore, using a more accurate half-life would likely reduce the 

RQs for mammals, but a dissipation study would be needed to acquire these data. 

However, even if data were available to reduce the foliar dissipation half-life used in 

the model, RQs would still likely exceed the LOC. 

• Moreover, there are no chronic RQ exceedances for risk to mammals from the 

degradate acifluorfen in all scenarios, except for the Florida fruiting vegetable use, 

where available use and usage data suggests there is little to no actual use, and one 

scenario 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. 

• 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, and 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). 

• 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. 

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Lactofen Case 7210 

www.rcgulations.gov Docket Number EPA-IIQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Proposed Interim Registration Review Decision 

Not all fish would be expected to be exposed to both I acto fen 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 uV-enhanced 

toxicity. The Agency also realizes many other factors can impact the amount ofuV 

light, such as time of day, time of year, stratospheric ozone and weather (cloud 

cover). 

• RQs are a conservative estimate of risk in that EPA selects the most sensitive 

toxicological effect from all available ecotoxicity studies. A vail able ecotoxicity 

studies often indicate less toxicity to test species than is assumed in EPA 's screeninglevel assessments. The toxicity endpoint used in risk assessment is chosen to 

represent a worst case toxicity scenario. 

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 

!acto fen use in the field. Additionally, data is available on the benefits of using lactofen 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 1% (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 totallactofen treated acres in 

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

the total acres treated with lactofen annually in the U.S. 

• Additionally, data suggest that average application rate used by growers for soybeans 

is 0.12 lbs. a.i./acre, whereas the ecological risk assessment used the maximum 

application rate of 0.2 lbs. a. i./acre. Moreover, the average application rate used by 

growers for peanuts is 0.17 lbs. a.i./acre, whereas the ecological risk assessment used 

the maximum application rate of 0.2 lbs. a.i./acre. 

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Lactofen Case 7210 

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Docket Number EPA-HQ-OPP-2005-0287 

Pesticide Re-evaluation Division 

Proposed Interim Registration Review Decision 

• 

• 

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 includes use 

of SLN products, show no usage for Florida fruiting vegetables for 1998-2012, 

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. 

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. 

With this use and usage information, combined with the conservative nature of the risk 

assessment and the aforementioned uncertainties, the Agency does not believe that potential 

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

4. Endangered Species Assessment 

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 of the National Academy of Sciences 

April2013 Report," dated November 1, 2013. 

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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 Proposed 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 !acto fen. 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. 

5. Endocrine Disruptor Screening Program 

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 chronic toxicity, including assessments of carcinogenicity, 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 lactofen, 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 11 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 hormonal 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 the E, A, or T effect. 

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

October 2009 and February 201 0, EPA issued test orders/data call-ins for the first group of 67 

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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, 2013 1 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 1 screening battery, please visit our website.2 

Lac to fen 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. 

IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION 

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this 

Proposed Interim Registration Review Decision. Except for the EDSP and ESA components of 

this case, the Agency has made the following Proposed Interim Registration Review 

Decision: (1) the Agency does not believe that potential ecological risks are of concern from the 

registered uses of lactofen, when taking into account the use and usage information and 

uncertainties outlined above, combined with the conservative nature of the risk assessment; (2) 

potential human health risks due to lactofen exposure are below the Agency's LOCs; (3) no 

additional data are required at this time; however, submission of a foliar dissipation study to the 

Agency would help to determine a more appropriate 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 proposed interim registration review decision, EPA is making no human health or 

environmental safety findings associated with the EDSP screening of lactofen, nor is it making a 

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

lactofen 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. Interim Registration Review Decision 

In accordance with 40 CFR sections 155.56 and 155.58, the Agency is issuing this 

proposed interim registration review decision document, and placing it in the lactofen 

registration review docket (EPA-HQ-OPP-2005-0287) for public comment for 60 days. A 

Federal Register Notice will announce the availability of this proposed interim registration 

review decision for I acto fen and initiate a 60-day public comment period. If there are no 

l See http://www.regulations.gov/#!documentDetail;D=EPA-HQ- OPPT-2009-047 7-0074 

for the final second l ist of chemicals. 

2 http://www.epa.gov/endo/ 

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significant comments or additional information submitted to the docket during the comment 

period that leads the Agency to change its proposed decision, EPA will issue an interim 

registration review decision for lactofen (case 721 0). 

B. Implementation of Mitigation Measures 

As stated in Section IV, no mitigation measures are required for I acto fen at this time. 

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