UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D

. C

. 20460

OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION

PC Code: 1289 31
DP Barcode: 40482 3
Date: March 24

, 20 1 6 MEMORANDUM

SUBJECT: Eco l ogical Risk Assessment for Dicamba DGA Salt and its O egra date, 3,6

- dichlorosalicylic acid ( D CSA)

, for the P roposed Post

- Eme rgenc e New Use on Oicamba

- Tolerant Cotton (MON 8770 I)

TO:

FROM:

THRU: Grant Rowland

, Risk Manager Re v ie wer Kathryn Montague

, Product Manager Team 23
Dan i e l Kenn y, Br anch Chief

H e rbicide Branch Registration Division (7505P) } / 

### I



### -**~** 

### 2-l/ 6

Michael Wagman, B iologist

# S.J,~**/.;7y/{c;** El i zabe th Donovan

, Biologist

### ~~~ 

## J (\ (

- I ' (

,...

### ~ 

## f ) )

. 2, \-\- \ 

### b
William P. Eckel, Ph.D., Senior Science

### Advi**or** 

## [1\1'\VL 

# /J.A nJY\

### ~ Amy Blankinship

, Senior Sc i ence Adv i sor (/ v 

# en /,

I

### ~/) Env ir onmental Risk Branch 6

### ~**~...-i--** /0. 

# o

Environmental Fate and Effects Divi sion (7507P)

Mark Corbin, Bran ch Chief

# ~u '? 1

, 

# \I b

Environmenta l Risk Branch 6 )- L.-\,.,1
Environmental Fate and Effects Di v i s ion (7

The Environmental Fate and Effects Division (EFED) has comp leted a review of the new use
requ est fo r the he r b i c i de di cam ha [M 1691 H erb i c i de, EPA Reg. No. 524-582 (58. l % diglycolamine
salt of dicamba ( DGA) ; P C code 128931 ) ] for post-emergent (in-crop) use on dicamba

- tolerant

cotton ( MON 88701, BOLLGARD II ® XTEN D FLEX rn cotton). Dicamba is currently registered
for u se o n cotton at application rates similar to those prop osed for the new u se as a pre-emergent
and post-harvest application, not to exceed 2 lbs a.e ./ A per year. The proposed new use is included

on th e supp lemental label ofM1691 h erbicide for pre-emergence and post-emergence (in

- crop ) use

on MON 8870 l dicamba-tolerant cotto n ; this ri sk assessment is based on t h e proposed l abe l dated
D ecember

, 20 1 5. The primary difference betwe e n the proposed new u se on MON 88701 cotton
and the cu rr en t r egistrat i on o n cotton i s the timing of app li cations. The p r opose d n ew u se allows

12 post

- emergenc e applications at a maximum single rate of 0.5 lbs a.e./A ; the total in

- crop rate (2 lbs a.e./A) is still enforced

. This ecological risk assessment only addresses the differences between what is currently registered and the change in the timing of applica tion and incorporates updated toxicological endpoint s

. References for a dditional d etails on the fate and transport properties and
effects data for dicamba are provided in the discussion below

.

Based on the proposed maximum application rates and exceed ances of the Agency’s Levels of Concern (LOCs)

, at the screening level there is a potential for direct adverse effects to Federally endangered and threatened (referred to hereafter as “ listed ”) and non

- listed birds (acute exposure only ), listed vascular a quatic plants, and li sted and non

- listed terrestrial dicots from the proposed

new use. This document does not make effects determinations for those taxa where the level of

concern for listed species has been exceeded

. Further evaluation of the potential fo r effects to listed species and modification of their critical habitat will be provided in another assessment.

Risks due to off

- site spray drift exposure and from runoff are detailed in the Risk Estimation and Characterization section below

.

While dica mba exists in either acid form or as one of several salts (including dicamba DGA),
b ridging data were submitted indicating that the dicamba salts will be rapidly converted to the free acid of dicamba (MRID 43288001). Additionally, submitted effects data i ndicate similar toxicity of the acid and salts (based on acid equivalents). EFED determined that fate studies conducted with dicamba acid provide “surrogate data ” for the dicamba salts and that toxicity data across the acid and salts could generally be co mbined (USEPA, 2005a)

.

Although the risks, based on standard risk assessment methods used by EFED, are not expected to differ from the previous assessment done for dicamba use on cotton (because the rates are similar to those already assessed), there is p otential for other ecological concerns that are characterized here, but were not evaluated in the previous assessment on conventional cotton . These concerns are related to a potential increase in usage of dicamba products

, the proposed changes in the timi ng of applications and the fate of dicamba and its metabolite, DCSA

, within dicamba

- tolerant cotton plants

. In general, there is also a potential for increased susceptibility of late season plants to direct impact from off

- site transport from volatilizati on related to dicamba use.

PROBLEM FORMULATION

Dicamba was first registered in the United States in 1967 and is widely used in agricultural,
i ndustrial

, and residential settings. Dicamba is a benzoic acid herbicide similar in structure and
mode of acti on to phenoxy herbicides. Dicamba controls annual, biennial and perennial broadleaf weeds in crops and grasslands, and it is used to control brush and bracken in pastures. Dicamba is formulated primarily as a salt in an aqueous solution. Supported forms are : dicamba acid ( PC code
0 29801), dicamba dimethylamine salt

- DMA ( 0 29802), diethanolamine salt (029803), dicamba sodium salt ( 0 29806), dicamba diglycoamine salt

- DGA (128931), dicamba isopropylamine salt (128944) and dicamba potassium salt (129043).

This assessment is for the new use request for M1691 Herbicide [ EPA Reg. No. 524

- 582 (56.8% diglycolamine salt of dicamba (DGA) ; PC code 128931)] for use on dicamba

- tolerant cotton (MON
87701 )

. Dicamba is currently registered for use on cotton at applic ation rates similar to those3 proposed for the new use. T he maximum registered application rate for cotton is 2.0 pounds acid equivalent per acre (lbs a.e./A) . For the proposed new use on dicamba

- tolerant cotton , the maximum single application rate is 1.0 lb s a.e. /A for a pre

- emergence application and 0.5 lb s a.e./ A for a post

- emergence application; the maximum seasonal rate is 2.0 lb s a.e./ A

.

The primary difference between the proposed new use and the current cotton registration is the timing of the app lications . T he current registration for dicamba on cotton is limited to pre

emergence and post

- harvest applications. T he proposed new use on dicamba

- tolerant cotton includes applications pre

- emergence and/or post

- emergence. The proposed post

- emergence

a pplications would occur later in the growing season than the current use pattern (but before post

harvest applications), which would increase the potential time period of exposure.

The major degradate under anaerobic conditions is 3,6

- dichlorosalicylic acid (DCSA) which is persistent, comprising > 60% of the applied after 365 days of anaerobic incubation in a sediment:pond water system (MRID 43245208). DCSA is also formed in aerobic soil under laboratory conditions at a maximum of 17.4 % of the applied parent. Toxicity data for DCSA
effects to mammals ha s been submitted to the Agency. No other toxicity data for DCSA has been submitted to the Agency. Based on available data, DCSA appears to be less toxic or equally toxic as the parent (see Table 1 ) for aquatic organisms on an acute basis , but may be substantially more toxic on a chronic basis to terrestrial organisms , specifically mammals

.

Therefore, this assessment will consider the parent and its degradate DCSA together in the aquatic

assessment (w ith the assumption that dicamba and DCSA are equa lly toxic) , while the terrestrial

assessment for mammals will consider parent dicamba and DCSA separately

.

Table 1 . Toxicity Data for Dicamba and its Degradate DCSA.

SOURCE DICAMBA DCSA SUBMITTED DATA ( Most Sensitive)

Acute oral Rat (LD 50 ; mg/kg

- bw) 2,740 2,641 (MRID 47899504)

Chronic rat (NOAEC; mg/kg

- bw) 136 (based on signs of parental neurotoxicity and

delayed sexual
maturation and decreased pup weight

at 450 mg a.e./kg

- bw) 8 mg a.e./kg

- bw (based o n decreased pup weight at 78 mg

a.e./kg

- bw , using
female lactation
doses ) (MRID 47899517) Acute oral Avian (LD 50 ; mg/kg

- bw) 188

-- Acute FW Fish (LC 50 ; mg/L) 28
Chronic FW Fish (NOAEC; mg/L)

-- -- Acute FW Invertebrate (EC 50 ; mg/L) 34.6

-- Chronic FW Invertebrate (NOAEC; mg/L)

-- -- NV Aquatic Plant (EC 50 ; mg/L) 0.061

-- V Aquatic Plant (EC 50 ; mg/L) >3.25

-- Acute Honeybees (LD 50 ; μg/bee) >90.65

-- Footprint WEBSITE 1 Acute oral Rat (LD 50 ; mg/kg

- bw) 1,581 >1,560 Acute oral Avian (LD 50 ; mg/kg

- b w) 1,373

-- Acute Fish (LC 50 ; mg/L) >100 >100 Chronic Fish (NOAEC; mg/L) 180

--4 Acute FW Invertebrate (EC 50 ; mg/L) >110.7 89 Chronic FW Invertebrate (NOAEC; mg/L) 97

-- NV Aquatic Plant (EC 50 ; mg/L) 1.8 138 V Aquatic Plant (EC 50 ; mg/L) >3.25 >73
Acu te Honeybees (LD 50 ; μg/bee) >100

-- Acute Earthworms (LC 50 ; mg/kg) >1,000 >1,000
1 Pesticide Properties Database (PPDB) ( http://sitem.herts.ac.uk/aeru/footprint/en/index.htm )
FW=freshwate r, NV=non

- vascular, V=vascular

BACKGROUND

The most recent regulatory actions for dicamba include the following:

• US EPA/EFED (201 4 ) Addendum to the Environmental Fate and Ecological Risk
Assessment for the Section 3 New Use of Dicamba on Dicamba

- Toler ant Soybean (MON 87708) Clarifying Plant Risks

. May 20 , 2014. D404138+.

• US EPA/EFED (2011) Ecological Risk Assessment for Dicamba and its Degradate, 3,6

- dichlorosalicylic acid (DCSA), for the Proposed New Use on Dicamba

- Tolerant Soybean (MON 87708). Marc h 8, 2011. D378444.

• US EPA/EFED (2010) Reduced Risk Request for Dicamba Herbicide Over

- The

- Top of
Dicamba

- Tolerant Soybean. May 27, 2010.

• US EPA. (2010) EFED Response to a FIFRA Section 18 Emergency Exemption for
Dicamba co

- formulate d with 2,4

- D (Latigo TM) Use on Tur f grown for grain, seed, and hay to control broadleaf weeds. Requested by the Oregon Department of Agriculture. May 24,
2010. D377095

• US EPA (2006) Reregistration Eligibility Decision for Dicamba and Dicamba Salts. June 8, 2006.

• US EPA (200 5 a ) EFED Reregistration Chapter for Dicamba/Dicamba Salts. August 31,
2005. D317696

• US EPA (2005 b ) Drinking water assessment for dicamba on sugarcane. May 31, 2005.
D317705

Consistent with the previous assessments, the environmental fate and effects dat a used in this

assessment are bridged across the dicamba acid and all of the supported dicamba salts (MRID 43288001). EFED established a strategy for bridging the environmental fate and effects data requirements for the dicamba sodium and potassium salts, dimethylamine salt (DMA), isopropylamine salt (IPA) and diglycoamine salt (DGA) to the dicamba acid. Bridging data were submitted indicating that the dicamba salts will be rapidly converted to the free acid of dicamba. Additionally, the submitted effe cts data indicate equa l toxicity of the acid and salts (based on acid5 equivalents). EFED determined that fate studies conducted with dicamba acid provide “surrogate data" for the dicamba salts and that toxicity data across the acid and salts could general ly be
combined. (USEPA, 2005a)

MODE OF ACTION

Dicamba is a benzoic acid herbicide similar in structure and mode of action to phenoxy herbicides. Like the phenoxy herbicides, dicamba mimics auxins, a type of plant hormone and causes abnormal cell growth by affecting cell division. Dicamba acts system i cally in plants after it is absorbed through leaves and roots. It is easily transported throughout the plant and accumulates in new
leaves.

USE CHARACTERIZATION

Monsanto Company submitted a new use reques t for the herbicide dicamba [ M1691 Herbicide, EPA Reg. No. 524

- 582 (56.8% diglycolamine salt of dicamba)] for use on dicamba

- tolerant cotton (MON 87701 )

. M1691 Herbicide is a water

- soluble formulation intended for control and suppression of many broadleaf weeds, woody brush and vines. Table 2 presents the proposed application rates to the dicamba

- tolerant cotton . Rates for dicamba salts are normalized to dicamba acid equivalent per acre (a.e./A).

Table 2. Dicamba DGA Proposed Use Pattern for Dicamba

- To lerant Cotton.

Crop Maximum Individual Application Rate 3
lbs dicamba a.e./A Number of Applications Application
instructions
and intervals (days) Max Annual Application Rate

in lbs dicamba

a.e./A/year Application
Method

Dicamba

tolerant

cotton MON 877 0 1 Pre

- emergence (pre

plant, at planting, or prior to crop emergence) 2 1.0 1 4 Pre

- plant, at planting, or prior to crop

emergence

. 1.0

2.0
total Restricted to ground sprays only Post

- emergence 1

(Preharvest) 0.5 4 4 From emergence to 7

days prior to

h arvest, minimum 7 days between applications 2 .0

1

- M1691 Herbicide

2

- Registered uses

3

- “Acid equivalent”

4

- Calculated by dividing the max application rate by the max individual application rate.

It is common for products like this to be tank mixed with other products and pesticide active ingredient s , but the label for this use prohibits tank

- mixing with other herbicides and only allows
tank

- mixes with products that have been tested and found not to increase the likekihood of drift/volatility. EFED recommends that additional guideline laboratory plant testing be required if proposed tank mixes include additional active ingredien ts to account for potential synergistic phytotoxic effects

. Testing of such products should include the standard suite of tested species from the already submitted dicamba and other active ingredient’s vegetat ive vigor studies as well as those that the op en literature and any other data that may indicate potential for synergistic effects.6 According to the proposed label, aerial application of dicamba to dicamba

- tolerant cotton is not permitted ( i.e., it is restricted to ground applications only ).

The p roposed dicamba registration is for use on dic amba

- tolerant cotton (MON 87701 ). Figure 1
shows acres of cotton harvested in 2014 in the U.S., per USDA. It is assumed that the new use of
dicamba on dicamba

- tolerant cotton would be within this 17

- state are a. The figure indicates that there were approximately 10 million acres of cotton harvested in 2014. The states shaded in red in the diagram below indicate a decrease in harvested cotton acres from the previous year while blue shading indicates an increas e in harvested acres from the previous year.

FIGURE 1. Acres of Cotton Harvested By State in the United States in 2014 (based on information from USDA

- NASS) http://www.nass.usda.gov/Charts_and_Maps/Field_Crops/cotnacm.asp

ENVIRONMENTAL FATE CHACTER IZATION

Dicamba is very soluble (6,100 ppm) and mobile (K oc = 13.4 L/mg o.c. ) in the laboratory, and is7 not expected to bioaccumulate in aquatic organisms as it is an anion at environmental pHs (pKa = 1.9). Dicamba is unstable to aerobic metabolism with half

- lives on the order of days, while it is generally stable to abiotic processes, and it is generally more persistent under anaerobic conditions. Dicamba may rea ch surface water via run

- off, spray drift during application

, and by vapor drift
from volati lization (see analysis below in the volatilization characterization)

. It is important to note
that m ultiple literature studies show that there is a high vapor drift from soybean fields resulting in

non

- target plant injury

. 1 Therefore

, an analysis of drift from particles volatilized from the treated field was completed (see below). Dicamba is less likely to be available to leach to groundwater
because it is so suscep t ible to aerobic degradation . H owever , a ny di camba reaching ground water would be som ewhat persistent (due to its relatively persistent anaerobic half

- life). The major route of exposure to non

- target organisms is likely spray drift and runoff. A refined characterization of potential exposure s from runoff , spray drift and volatility is pr esented in this assessment. Available incident reports indicate that visual observations of off

- field plant damage have followed dicamba applications and subsequent spray drift and/or volatilization of dicamba residues (discussed below
in the incident cha racterization section)

.

The major degradate under anaerobic conditions is 3,6

- dichlorosalicylic acid (DCSA), comprising > 60% of the applied after 365 days of anaerobic incubation in sediment

- pond water system (MRID 43245208). DCSA is no t persistent when formed under aerobic conditions and degrades roughly at the same rate as the parent (8.2 days, MRID 43245207). DCSA was also found in the two acceptable field studies in soil segments deeper than 10 cm, and is believed to be persistent if it was
to reach anaerobic ground water. This degradate was formed in aerobic soil under laboratory conditions at the maximum of 17.4 % of the applied parent. Other minor dicamba degradates of
concern are DCGA and 5

- OH

- dicamba, and both are less toxic than the parent and DCSA. The formation of DCGA in the laboratory studies did not exceed 3.64%, and the formation of 5

- OH dicamba did not exceed 1.9 % in soil/water system during anaerobic aquatic degradation of dicamba under laboratory condition. DCSA was also a major meta bolite in plant metabolism and magnitude of residue studies for dicamba

- tolerant soybean and cotton.

Chemical structures of dicamba and dicamba salts are presented in USEPA, 2011 . Further details regarding fate and transport laboratory and field studies submitted for dicamba can be found in (US EPA, 2005 (EFED Reregistration Chapter); USEPA, 2011)

.

Aquatic Exposure Estimates

Tier II modeling was performed for dicamba acid and its major degradate DCSA using the Surface Water Concentration Calculator ( SWCC v1.106 ) coupled with the standard pond scenario. The

s tandard Mississippi cotton scenario was selected to assess runoff potential from vulnerable use sites. The modeling scenario for DCSA was based on the following: (1) assuming 17.4% conversion from parent to DCSA and (2) using molecular weight conversion to adjust from parent application rate to DCSA application rate. Tables 3 and 4 list the input parameters used for the PRZM/EXAMS modeling of dicamba ac id and DCSA degradate.

Table 3

. SWCC Input Parameters for Parent Dicamba.

1 Al

- Khatib and Tamhane, 1999; Auch and Arnold, 1978; Everitt and Keeling, 2009; Kelley et al., 2005; Hamilton and Arle, 1979; Lanini, 2000; Marple et al., 2008; Wall, 1994; Weidenhamer et al., 1989; Wax et al., 1969.8 Model Input Variable Input Value Source and Comments
Application rate (kg ai/hectare) 1.12; 0.56; 0.56 M1691; EPA Reg. No. 524

- 582

Number of appl./season 3 M1691; EPA Reg. No. 524

- 582

Interval between appl i cations 7 days M1691; EPA Reg. No. 524

- 582

Application Method Ground M1691; EPA Reg. No. 524

- 582

Scenario modeled (Metfile)

- Initial Application Date MScottonSTD (W03940.dvf)

- 16 April Dates based on the crop profile, d ate of planting, & precipitation data.

Henry’s Law Constant (atm

m 3 /mol) 1.6 x 10

- 9 Estimated (VP x MW)/(760 torr/1 atm * solubility)
Molecular Weight (g/mol) 221 SANDOZ Safety Data Sheet (Nov, 1989).
Solubility @ 25°C (mg/L) 6100 SANDOZ Safety Data She et (Nov, 1989).
Vapor Pressure (torr) 3.41 x 10

- 5 SANDOZ Safety Data Sheet (Nov, 1989).

K oc (mL/g o.c. ) 13.4 (average) MRID 42774101

Aerobic Soil Metabolic Half

life (days) 18 MRID 43245207; (6d x 3)

Aerobic Aquatic Metabolic
Half

- life (days) 72.9 MRID 43758509; 3x a singl e half

- life value of 24.3 days
Anaerobic Aquatic Metabolic
Half

- life (days) 423 A single half

- life value was available (MRID 43245208); 3x the half

- life value (141 x 3 = 423)
Hydrolysis (pH 7) half

- life (days) 0 Stable. MRID 405479 02

Aquatic Photolysis Half

- life (days) 105 MRID 42774102. Adjusted half

- life to represent sun intensity and 12 hours of sunlight per day. 38.1 day value represented continuous sun exposure at an intensity of 1.38 times natural sunlight.

Table 4

. SWCC I nput Parameters for DCSA. Model Input Variable Input Value Source and Comments
Application rate (kg ai/hectare) 0.18; 0.09; and 0.09 (degradate molecular weight)/(parent molecular weight) x max%formation x application rate = (207/221)x 0.174

x 1.12

Numbe r of appl./season 3 EPA Reg. No. 524

- 582

Interval between appl. (d) 7 days EPA Reg. No. 524

- 582

Scenario modeled (Metfile)

- Initial Application Date MS cotton STD (W03940.dvf)

- 16 April Dates based on the crop profile, date of planting, & precipitation d ata.

Henry’s Law Constant (atm

m 3 /mol) 1.6 x 10

- 9 Estimated for dicamba and used for DCSA

Molecular Weight (g/mol) 207 Product Chemistry9 Model Input Variable Input Value Source and Comments
Solubility @ 25°C (mg/L) 2112 MRID 43095301
Vapor Pressure (torr) 3.41 x 10

- 5 For Dicamba

K oc (mL/g) 1208 (average ) MRID 43095301

Aerobic Soil Metabolic Half

life (days) 24.6 MRID 43245207; (8.2 d x 3)

Aerobic Aquatic Metabolic
Half

- life (days) 49.2 No acceptable data were available; 2x the half

- life corresponding to the PRZM aerobic soil metabolism rate input valu e (2x 24.6d)
Anaerobic Aquatic Metabolic
Half

- life (days) 0 Stable. MRID 43245208.

Hydrolysis (pH 7) Half

- life (days) 0 Stable. MRID 43245208

Aquatic Photolysis Half

- life (days) 105 No data for DCSA; therefore, used value for
dicamba

.

SWCC Modeling O utput

Table 5 presents combined SWCC estimated environmental concentrations in surface water for dicamba acid and the DCSA degradate for the proposed use on dicamba

- tolerant cotton

. These estimated environmental concentrations (EECs) were used to calcula te risk to aquatic animals and plants.

TABLE 5 . Combined SWCC Estimated Environmental Concentrations (EECs) for Dicamba Acid and DCSA Degradate.
Scenario 1

- in

- 10

- year Peak
EEC 1

- in

- 10

- year 21

- day mean EEC 1

- in

- 10

- year 60

- day mean EEC
MS cotton 42.6 ppb 40.4 ppb 35.8 ppb

EEC s re presents a combined value for the parent and degradate

Terrestrial Exposure Estimates

Dicamba

- specific Half

- Life and Parent Dicamba Exposure Estimates

In the risk assessment for the proposed new use on soybeans (USEPA, 2011), EFED modeled the dicamba residues using a single application (the T

- REX model available at the time of the assessment was incapable of running applications with variable rates) and used the default foliar dissipation half

- life value of 35 days. For th is cotton new use risk assessment, EFED has refined the estimates of exposure by modeling the residues using the maximum potential application rates with minimum application intervals (a 1 lb a. e ./A application followed by two 0.5 lb a. e ./A applicati ons with a seven day interval between each application) and a chemical

- specific foliar dissipation half

- life value for parent dicamba

.

EFED used residue data by Jimenez (1994; MRID 43370701) to calculate a dicamba specific foliar dissipation half

- life. According to the available Health Effects Division (HED) review (DP Barcode 207649, 3/11/1996), this study was acceptable for use in risk assessment and indicated that10 there was no difference in foliar dissipation data between the various tested dicamba sa lt formulations (DMA, DGA and sodium salt formulations). Therefore, data for all dicamba salt
formulations tested were used to calculate the final foliar half

- life value.

Half

- lives were calculated for each set of residue decline data based on the NAFTA Guidance for Evaluating and Calculating Degradation Kinetics in Environmental Media and using the PestDF package in the R statistical program. Each equation was evaluated for appropriateness before
inclusion in the final half

- life calculation. Individual decline data and estimated foliar half

- life
values are available in Table 6

. A summary of this information is provided in the table below. The upper 90 th percentile, one tailed, confidence interval of 8.4 days was used to calculate refined EECs
in this a ssessment.

Table 6 . Dicamba Half

- Life (days) in Foliage
Arithmetic
Mean Standard
Deviation Max Value Min Value Number of
Values Upper 90%
CL on the

mean 7.3 6.6 43.7 1.11 99 8.4

Exposure estimates for terrestrial animals assumed to be in the target area or in an area exposed to spray drift are derived using the T

- REX (Terrestrial Residue EXposure model) model (version 1.5.2., 6/11/2013). This model incorporates the Kenaga nomograph, as modified by Fletcher et al. (1994), which is based on a large set of actual field residue data. The upper limit values from the nomograph represent an approximation of the highest residue value observed in the data set (Hoerger and Kenaga 1972). Consideration is given to different types of feeding strategies for
mammals and birds; including herbivores, insectivores and granivores. For dose

- based exposures, three weight classes of birds (20, 100, and 1000 g) and mammals (15, 35, and 1000 g) are
considered. The dicamba

- specific foliar dissipation half

- life of 8.4 days was used for risk estimation. The assessment assumes a maximum single application rate of 1.0 lb a. e ./A followed by two 0.5 lb a. e ./A applications with a 7 day application interval to estimate terrestrial exposures
of dicamba. The dose

- and dietary

- based EE Cs (upper bound Kenaga) on a variety of food items
from the use of dicamba applied at the maximum label ed rate s i s provided in Appendix 1 , along
with the full T

- REX inputs and output

.

DCSA Metabolite Exposure Analysis

The available data indicate that in mammals, DCSA has similar acute toxicity as parent dicamba, but is substantially (17x) more toxic on a chronic basis

. DCSA residues following dicamba applications prior to planting conventional cotton are generally considered negligible and would not
be of concern (USEPA, 1983 and 1984) . However, in dicamba

- tolerant cotton plants, DCSA can form in greater amounts ( MRIDs 48728701 & 48728703 ) . Based on the available data, EFED evaluated the DCSA metabolite separately from parent dicamba in the chronic terres trial effects

assessment.

Appendix 2 shows residues of dicamba and its metabolites in cotton plants following a number of different treatment regimes (data from MRIDs 48728701 & 48728703). The highest residues for
both dicamba and its metabolite DCSA w ere found in cotton gin byproducts following TRT 4 (411 post

- emergent applications of 0.5 lb/A for a total seasonal application rate of 2.0 lb/A) where maximum DCSA residues were approximately 21% of the maximum total dicamba

- related residues (6.29 ppm DCSA compared to 23.6 ppm dicamba) while undelinted cotton seed had substantially less residues (0.27 ppm DCSA and 1.54 ppm dicamba)

. EFED used the maximum values from the empirical data on gin byproducts and undelinted cotton seeds to assess risk from DCSA re sidues following post

- emergent applications of dicamba on DT

- cotton plants to terrestrial vertebrates. Gin byproducts for cotton can include a number of different plant parts including fragments of burs,
stems and leaf material and immature cotton seed. Si nce gin byproducts can include various plant parts including immature seeds and since the mature seeds had very low measured DCSA residues (thereby, the immature seeds could potentially be influencing the overall residue concentration when using all gin by products) , it is possible that the maximum DCSA residues in cotton plant
tissue s may be slightly higher. Additional data on the distribution of DCSA residues in the various cotton plant parts ( e.g. stem, leaves) over a broader temporal range would decreas e this uncertainty. However, the best available data indicate that DCSA is a much smaller fraction of dicamba related
residues in the DT

- cotton system and using the maximum empirical residues is considered a conservative approach

.

Based on the ava ilable plant metabolism data for DCSA on non

- DT plants, EFED assumed that any exposure for terrestrial vertebrates occurs as a result of feeding solely on DCSA in DT

- cotton and no exposure to DCSA is expected for terrestrial vertebrates feeding off the fie ld, even if dicamba residues should occur following spray drift or volatilization.

ASSUMPTIONS AND UNCERTAINTIES

DCSA percent formation used for the modeling “application rate” calculation was based on the amount of degradate formed in the aerobic soi l metabolism conducted on silt loam soil. It is possible that DCSA may be formed in different amounts in different soil types, and could result in DCSA EECs being under

- or over estimated.

ENVIRONMENTAL EFFECTS DATA

Assessment of risk is based on the most sensitive species tested for terrestrial and aquatic organisms. The acute and chronic toxicity values for the most sensitive terrestrial and aquatic organisms tested are presented in Table 7 . These endpoints are based on those presented in the

most recent assessment conducted for dicamba (USEPA 201 1 , D 378444 ) , except for the terrestrial plant endpoints for dicamba DGA and the chronic mammalian endpoint s for dicamba acid and the
metabolite DCSA

.

The risks to terrestrial plants were evaluated using new toxicity information from seedling emergence (MRID 47815101) and vegetative vigor (MRID 47815102) terrestrial plant studies conducted with a typical end

- use product (TEP) representative of the product being proposed here
for use on dicamba

- tolerant soybean. The new vegetative vigor study was classified as

“ supplemental ” due to a decrease in plant height in lettuce controls. Quantitative data for the other nine species in the study may be used in risk assessment, but the endpoints for lettuce may no t be
used quantitatively in risk assessment. However , the qualitative data in MRID 47815 1 02 indicate12 that the endpoints for this species are likely not as sensitive as the quantitative endpoint for the most sensitive species, soybean (plant height). The new data indicate s that the DGA salt may be
less toxic to monocots than dicots , but has an EC 25 approximately 13 times more toxic to the vegetative vigor of dicots than dicamba acid. It is unclear if the enhanced toxicity to dicots is due to synergistic e ffects with surfactants and adjuvants in the formulation used (Clarity Herbicide, EPA Reg No. 7969

- 137, 56.8% DGA salt) or due to the DGA salt itself.

The screening

- level risk assessment for the proposed new use on soybeans (USEPA, 2011. D378444) used t he chronic endpoint from the rat 2

- generation study (MRID 43137101), a NOAEL of 45 mg/kg

- bw, based on decreased pup weight at 136 mg/kg

- bw compared to the concurrent
controls. The Health Effects Division ( HED ) recently reanalyzed the data from this study (USEPA,
2016 a ; D431873 ) in comparison to the historical control database range and determined that the NOAEL and LOAEL should be raised to 136 and 450 mg/kg

- bw, respectively

, because pup weights in each generation in the 136 mg/kg

- bw treatment group were w ithin the historical control range and above the historical control mean for the F1, F2A and F2B generations.

The screening

- level risk assessment for the proposed new use on soybeans also used data from a preliminary review of a rat 2

- generation study w ith DCSA (MRID 47899517) which identified a chronic NOAEL endpoint of 37 mg/kg/d based on decreased parental bodyweight in the 362 mg/kg/d treatment group. However, since that assessment was completed , the chronic endpoint was
revised in the final DER revi ew (USEPA, 2012) and a recent memorandum for a benchmark dose analysis (USEPA, 2016 a ) to reflect the observed statistically significant decreases (6

- 9%) in offspring weight on 14 and 21 post

- natal days (PND). The DER review from 2012 considered the
LOAEL f rom effects to pup weight to be based on the male pre

- mating dose of 37 mg/kg/d, with a corresponding NOAEL of 4 mg/kg/d. The recent benchmark dose analysis conducted by HED ( USEPA, 2016 a ) determined BMD 5 (estimated benchmark dose (BMD) to result in 5% bod y weight change in pups f rom background levels) and BMDL 5 (the lower 95% confidence level on
the BMD 5 ) based on both the male pre

- mating dose and the female lactation dose and noted that female lactation doses are more reflective (than male

- premating doses ) of pup exposure during the nursing period when the pup body weight decreased. This analysis concluded that the pup weight LOAEL and NOAEL threshold values based on the dam lactation doses would be 78 mg/kg/d and 8 mg/kg/d , respectively . HED also calcul ated a BMD 5 (estimated benchmark dose to result in 5% body weight change in pups from background levels) and BMDL 5 (the lower 95% confidence level
on the BMD 5 ) of 38.6 and 34.9 mg/kg/d, respectively

, based on the female lactation doses. In the
revised ana lysis below, EFED used the NOAEL value of 8 mg/kg/d for risk estimation and further
characterized the risk using the BMDL 5 of 34.9 mg/kg/d for DCSA effects to mammals.

No chronic data is available for the effects of the DCSA degradate to birds (or rept iles or terrestrial

phase amphibians, for which birds are surrogates). As a highly conservative approach, EPA will consider the toxicity differential for chronic effects between parent dicamba and the metabolite DCSA and apply a similar ratio to estimate chronic effects to avian organisms. Therefore, a factor of 17x (based on the chronic endpoints of 136 mg/kg

- bw for parent dicamba and 8 mg/kg

- bw for DCSA) is applied to the dicamba chronic NOAEC of 695 mg/kg

- diet for the mallard duck, to result in a highl y conservative estimate of a chronic NOAEC of 40.9 mg/kg

- diet for birds for DCSA. This is considered a highly conservative approach as the chronic mammalian endpoint is based on effects to pups who would have been continually exposed to DCSA residues in ut ero and13 throughout lactation while chicks in the avian reproduction test would not be exposed to DCSA residues while still in the egg or post hatch.

TABLE 7 . Toxicity Values Used to Assess Risks from Use of Dicamba and its Metabolite, DCSA

. Test substanc e was dicamba DGA unless otherwise noted in the footnotes.

SPECIES ACUTE ENDPOINT Chronic Endpoint MRID
Rainbow trout ( Oncorhynchus mykiss ) LC 50 = 28 mg a.e./L 4 No data available 40098001 1

Fathead minnow ( Pimphales promelas ) LC 50 > 56.4 mg a.e./L 5 NOAEC = 9. 7 mg a.e/L 4 48718010 2 , 48718008 2

Sheepshead minnow ( Cyprinodon variegates ) LC 50 > 180 mg a.e./L NOAEC = 11 mg a.e./L 4 000253901 , 48718011 2

Water flea ( Daphnia

magna ) EC 50 > 100 mg a.e./L NOAEC = 42 mg a.e./L 5 40094602 , 48718007 2

Grass shrimp ( Pala emonetes purgio ) EC 50 > 100 mg a.e./L No data available 00034702

Mysid shrimp No data available NOAEC = 11 mg a.e./L 4 48718012 2 Duckweed ( Lemna gibba ) IC 50 > 3.25 mg a.e./L NOAEC = 0.20 mg a.e../L 42774111
Blue

- green algae ( Anabaena flos

- aquae ) IC 50 = 0 .061 mg a.e./L NOAEC = 0.005 mg a.e./L 42774109

Green algae ( Pseudokirchneriella subcapitata ) IC50 = 7.01 mg a.e./L 5 EC 05 3 = 0.39 mg a.e./L 5 48718009 2

Bobwhite quail ( Colinus virginianus ) or Mallard duck ( Anas platyrhynchos ) LD 50 = 188 mg a.e./kg

- bw (qua il)
LC 50 > 10,000 mg a.e./kg

diet (quail) NOAEC = 800 mg a.e./kg

diet (duck) (based on a reduction in hatchability at 1,600 mg a.e./kg

- diet) 42918001, 00025391,
43814003

Zebra finch ( Taeniopygia
guttata ) LD 50 = 207 mg a.e./kg

- bw 4 No available data 4871801 3 2

Rat ( Rattus norvegicus ) LD 50 = 2,740 mg a.e./kg

bw NOAEL = 136 mg a.e./kg

bw (based on neurotoxicity and delayed maturation in parent generation, decreased pup weight at 450 mg a.e./kg

bw) 00078444, 43137101

Rat ( Rattus norvegicus ) LD 50 = 2,641 6 NOAE L = 8 mg a.e./kg

bw (based on decreased pup weight at 37 mg ae/kg

- bw 6

. 47899504 , 47899517

Honey bee ( Apis mellifera ) LD 50 > 91 μg a.e./bee No data available 00036935 Dicot ( Tomato, Lycopersicon esculentum )

– seedling emergence EC 25 = 0.123 lbs ae/A NOAE C = 0.0673 lbs ae/A 47815101

Monocot ( Onion, Al lium

cepa )

– S eedling
E mergence EC 25 = 1.68 lbs ae/A NOAEC = 0.64 lbs ae/A 47815101

Dicot ( Soybean, Glycine

max )

– V egetative V igor EC 25 = 0.000513 lbs ae/A NOAEC = 0. 000 261 lbs
ae/A 47815102

Monocot ( Onion

, Allium

cepa )

– V egetative V igor EC 25 = 0.472 lbs ae/A EC 05 = 0.137 lbs ae/A 47815102

1 The raw data from this study (Mayer and Ellersieck, 1986; MRID 40098001) were not available for review. Therefore, per current EFED policy regarding the results fro m this study, the study was classified as ‘supplemental’.

2 Currently in review.14 3 EC 05 value was used in lieu of non

- definitive NOAEC.

4 Test material was dicamba acid.

5 Test material was dicamba BAPMA salt.

6 Test material was DCSA “a.e.” = acid equ ivalent.

RISK ESTIMATION & CHARACTERIZATION

Aquatic Organisms

The aquatic assessment used a total toxic residues (TTR) approach to evaluate risk from dicamba
and its metabolite DCSA. An RQ was calculated for aquatic animals based on available data for freshwater fish [specifically rainbow trout ( Oncorhynchus mykiss ) (MRID 40098001)]. The acute RQ for freshwater fish is <0.01 for both dicamba ( 42.2 μg a.e./L divided by 28,000 μg a.e./L) and DCSA ( 0 .4 μg a.e./L divided by 28,000 μg a.e./L) , which is belo w the acute LOC (0.5) . The results from the remaining acute aquatic animal studies are from limit tests and are non

- definitive ( i.e ., the
LC 50 /EC 50 ’s are ‘greater than’ values); therefore, acute RQs were not calculated using these data.

In order to gai n a better understanding of how the EECs for the maximum proposed dicamba application rate for cotton relate s to the toxicity data currently available for aquatic animals, we compared the EECs to the toxicity endpoints using the conservative assumption tha t the highest concentrations tested in the acute aquatic animal studies represent endpoints ( e.g ., acute: LC 50 /EC 50 = 100 mg a.e./L). This is conservative as it assumes that at that dose, 50% of the animals would not have survived, however in these studie s there was either no mortality or substantially less than 50% mortality at this dose. In this exercise, none of the acute RQs for estuarine/marine fish or aquatic invertebrates (freshwater and estuarine/marine) would exceed an Agency level of concern (LO C) for dicamba or DCSA (they are all <0.01).

C hronic RQ s for both the fathead minnow and sheepshead minnow would be <0.01

, which is well below the level of concern (1.0). However, acute toxicity data indicates rainbow trout are more sensitive than fathe ad and sheepshead minnow s (LD 50 of 28 mg ae/L for trout compared to >56.4
for the fathead minnow and >180 mg ae/L for the sheepshead minnow ) . However, the rainbow
trout would have to be more than 270 times more sensitive than the fathead minnow on a chron ic
basis to result in an exceedance of the chronic LOC. Given that the acute data indicates that dicamba is only slightly toxic to rainbow trout, the likelihood that dicamba is more than 2 orders of magnitude more sensitive on a chronic basis to rainbow t rout compared to minnow s is considered
low. The chronic RQ for aquatic invertebrates is <0.01 based on the most sensitive aquatic invertebrate endpoint of 11 mg ae/L for mysid shrimp.

For aquatic plants the only RQ that exceeds an Agency LOC is for liste d non

- vascular aquatic plants for parent dicamba (RQ = 8. 5 ) (see Table 8 ). RQs for non

- listed non

- vascular aquatic plants
and listed and non

- listed vascular aquatic plants would all be below the LOC of 1.0.15 TABLE 8 . RQs for Aquatic Plants and the Us e of Dicamba on Cotton

.

TAXON LISTED/NON

LISTED ENDPOINT (μg a.e./L) Combined DICAMBA and DCSA Degradate

EEC (μg a.e./L) RQ

Vascular Aquatic
Plant Non

- listed species IC 50 > 3,250 42.6 (peak) <0.013

Listed species NOAEC = 200 42.6 (peak) 0.2 1

Non

- V ascular Aquatic Plant Non

- listed species IC 50 = 61 42.6 (peak) 0.7

Listed species NOAEC = 5 42.6 (peak) 8. 5 Bolded numbers exceed the Agency LOC of ‘1’. “a.e.” = acid equivalent. “N/A” = not applicable

Terrestrial Organisms

Assessment for Exposure to Dicamba Residues

Birds

The maximum single application rate for the proposed new use of dicamba on dicamba

- tolerant

cotton is 1.0 lb a.e./ A , with a maximum yearly application rate of 2.0 lb s a.e./ A . The maximum single application rate of 1.0 lb a.e./ A c an only be used once; the maximum application rate for subsequent applications is limited to 0.5 lb s a.e./ A

. EFED used T

- REX version 1.5.2 to simulate applications of 1 lb a.e. /A , followed by two 0.5 lb s a.e./ A at seven

- day intervals, with a n 8.4

- day
dica mba

- specific foliar dissipation half

- life.

In the previous assessmen ts conducted by EFED (USEPA, 2005, 201 1 ), there were risks to birds (acute

- listed and non

- listed) and mammals (acute

– listed; chronic

– listed and non

- listed)
identified based on LOC exceedances from RQs calculated in T

- REX using the 2.0 lb s a.e./ A application rate. At the 1.0 plus 0.5 plus 0.5 lb a.e./ A application rate s , the Agency’s acute LOCs
are exceeded for listed and non

- listed birds [acute dose

- b ased RQs range from <0.01 ( large

g ranivore birds ) to 2.21 (small bird s consuming short grass)] (see Table 9 and APPENDIX 1 ). No chronic RQs exceed the Agency’s LOC for chronic risk (chronic dietary

- based RQs range from
0.02 to 0.3 8 ).16 TABLE 9 . Acute Dose

- Based RQs for Birds fr om T

- REX 1.5.2 for Dicamba Use on Dicamba

Tolerant Cotton

.

Dose

- based RQs (Dose

- based EEC/adjusted LD50) Avian Acute RQs Size Class (grams)

20 100 1000

Short Grass 2.21 0.99 0.31

Tall Grass 1.01 0.45 0.14 Broadleaf plants 1.24 0.56 0.18 Fruits/pods/s eeds/ 0.14 0.06 0.02
Arthropods 0.87 0.39 0.12 Seeds (granivore) 0.03 0.01 <0.01
Bolded numbers exceed the Agency’s acute risk LOC for non

- listed species (RQ > 0.5) and bold italicized numbers
exceed the acute risk LOC for listed species (RQ > 0.1).

Ma mmals

For mammals, none of the acute RQs from exposure to dicamba exceed any of the Agency’s LOCs (acute dose

- based RQs range from <0.01 to 0.04 for dicamba ). Additionally, none of the dietary

based chronic RQs exceed the Agency’s LOCs for chronic risk ( chronic dietary

- based RQs range
from 0.0 1 to 0. 10 for dicamba ). Chronic dose

- based RQs also do not exceed the Agency LOC for chronic risk from dicamba (RQs range from 0.01 to 0.84 ; see APPENDIX 1 )

.

DCSA Chronic Effects Assessment for Terrestrial Organism s

No effects data are available for the chronic effects of DCSA to birds. EFED conservatively assumed that the ratio of parent dicamba to DCSA toxicity ( 17 x differential) from the mammalian toxicity data could be applied to the chronic effects endpoint fo r birds. However, since the DCSA chronic endpoint for mammals is based on effects to pups who were continually exposed in utero and throughout lactation in the study, it may be conservative to assume that this toxicity differential in mammals for parent d icamba and DCSA would be equivalent for chicks who in an avian reproduction test would have been presumed to not be exposed to DCSA residues during their gestation in the egg (beyond initial maternal transfer into egg during egg development) or post

hatch

.
Empirical data for DCSA are available from magnitude of residue studies reviewed by HED (MRIDs 48728701 and 48728703) for dicamba pre and post

- emergent applications (4 applications at a total of 2.0 lbs a.e./A, 4 different treatment groups with diff ering timing of applications) . This
data show dicamba and DCSA residues in undelinted cotton seed and gin byproducts (residual cotton plant parts) had maximum residues of 23.6 mg/kg

- diet ( ppm ) dicamba and 6.29 ppm DCSA
at 6

- 7 days following the last application. Using the maximum DCSA residues in gin byproducts ( 6.29 ppm ) or undelinted cotton seed (0.27 ppm) wo uld not result in an exceedance of the chronic LOC for any size class of mammal or bird (RQs would range from <0.01

— 0. 34 ; Table 10 )

. Residues in arthropods (as a dietary item for birds and mammals consuming insects that have
consumed cotton tissues with D CSA residues) were assumed to follow the Kenaga nomogram relationship between broadleaf plants and arthropods and therefore were considered to contain 4.4 ppm which also would not result in any exceedances (RQ ’s range from 0.11

— 0.24 )

.17 While this assessme nt used the comparison of the maximum residues detected with the chronic mammalian endpoint, there is some uncertainty due to the limited temporal sampling of DCSA
residues in DT

- cotton tissues (only measured at one time point) and therefore understanding formation/decline rates is not possible (to better understand potential maximum residues). Plant
metabolism studies that track DCSA residues over time in all parts of DT

- cotton plants following post

- emergent applications would decrease this uncertainty

. In the absence of this, EFED has used the best available data and the maximum measured residues to evaluate the chronic exposure. T his risk estimation uses the NOAEC endpoint of 8 mg/kg/d. If the BMDL 5 of 34.9 mg/kg/d for DCSA
effects to mammals calcula ted by HED were used instead, than the maximum chronic RQ would be
0.08

. Given that the maximum measured DCSA residues are not close to the NOAEC threshold endpoint (max RQ of 0.34) and the BMDL 5 indicates that biological effe cts may not be expected

even if residues were an order of magnitude higher than indicated by the maximum measured residues, the lack of a plant metabolism study tracking DCSA residues throughout the DT

- cotton plant may not be considered a major uncertainty.

Table 10 . Dose

- based exp osure, body

- weight adjusted chronic endpoints and risk quotients for mammals consuming DT

- cotton tissues containing DCSA residues (max empirical values of 6.29 mg/kg in broadleaf plant tissue (gin byproducts), 0.27 mg/kg in seeds)

Size Class (g) Dietary It em Food Intake (k

- diet/d) Dose

- based EEC (mg/kg

- bw) Adjusted NOAEL (mg/kg

- bw) RQ

Small (15g) Broadleaf plant 0.0143
58.25 17.58 0.34

Seed 0.00318 0.09 17.58 < 0.01 Arthropod 0.0143 4.19 17.58 0.24
Medium (35g) Broadleaf plant 0.0231
40.33 14.23 0. 29

Seed 0.00513 0.06 14.23 < 0.01 Arthropod 0.0231 2.90 14.23 0.20 Large (1000g) Broadleaf plant 0.153 9.35 6.15 0.16

Seed 0.0340 0.01 6.15 <0.01 Arthropod 0.153 0.67 6.15 0.11

Table 11 . Dose

- based exposure and risk quotients for birds consuming DT

- cotton tissues containing DCSA residue s (chronic endpoint assumes a 17 x differential in toxicity between parent dicamba and DCSA to birds).

Size Class (g) Dietary Item Food Intake (k

- diet/d) Dose

- based EEC (mg/kg

- bw) NOAEC (mg/kg

- bw) RQ

Small (20g) Broadl eaf plant 0.0228 7.17 40.88 0.18

Seed 0.0051 0.07 40.88 <0.01 Arthropod 0.0228 5.02 40.88 0. 12
Medium (100g) Broadleaf plant 0.0649 4.08 40.88 0.07

Seed 0.0144 0.04 40.88 <0.0118 Size Class (g) Dietary Item Food Intake (k

- diet/d) Dose

- based EEC (mg/kg

- bw) NOAEC (mg/kg

- bw) RQ

Arthropod 0.0649 2.86 40.88 0.14 Large (1000g) Broadleaf plant 0.291 1.83 40.88 0.04

Seed 0.065 0.02 40.88 <0.01 Arthropod 0.291 1.28 40.88 0.0 3

Beneficial Terrestrial Invertebrates

The initial 2011 risk assessment for dicamba use on tolerant plants (soybean use D378444, 3/8/2011) was conducted prior to EPA develop ing methods to quantitatively evaluate risks to pollinators. Consequently, that assessment included no quantitative analysis of the risk to beneficial terrestrial invertebrates posed by dicamba use patterns. Based on the acute contact data for the honey b ee, the 2011 assessment qualitatively concluded that direct effects to listed terrestrial insect species were not expected.

In June 2014, President Obama issued a memorandum 2 establishing a Pollinator Health Task Force,

co

- chaired by USDA and EPA, to crea te a National Pollinator Health Strategy that promotes the health of honey bees and other pollinators (including birds, bats, butterflies, and insects).
Consistent with this Presidential memorandum

, the Office of Pesticide Programs (OPP) has been
evaluati ng its own risk assessment methods to more quantitatively characterize pesticide risks to bees. This evolution has identified additional honeybee life stage testing and longer duration effects tests for adults (i.e., larval acute and chronic studies, and adult chronic studies) as potentially important to the risk assessment process.

This assessment explains additional lines of evidence not considered in the 2011 risk assessment to better characterize the risk posed by dicamba uses to terrestrial inverte brates and ascertain if the lack of additional bee studies (including chronic adult honey bee data and acute and chronic larval honey bee data) is a significant limitation to making a more definitive characterization. The
characterization of the chronic r isks to adult and larval bees presented here is a novel approach using the best available data. However, this approach is not meant to preclude potential requests for additional terrestrial invertebrate data or represent a new framework for EPA assessment s for estimating potential risks to beneficial terrestrial invertebrates. EPA’s established methodology for evaluating risks to pollinators can be found in the Guidance for Assessing Pesticide Risks to Bees (USEPA, 2014) and relies on a full suite of honey bee laboratory data including acute and chronic effects studies to adult and larval honey bees to fully estimate risk to bees.

Acute Contact and Dietary Exposure to Adult Honey Bees

On an acute contact exposure basis, dicamba is classified as ‘practica lly non

- toxic’ to non

- target insects including honey bees (honey bee acute contact LD 50 > 91 μg a.e./bee (MRID 00036935). If

2 h ttps://www.whitehouse.gov/the

- p ress

- office/2014/06/20/presidential

- memorandum

- creating

- federal

- strategy

promote

- health

- honey

- b19 an RQ were calculated for terrestrial invertebrates, 3 using this non

- definitive LD 50 (conservatively assuming that the highest t ested dose would result in 50% mortality where in that study, mortality at that dose was only 2.5%) and determining acute contact exposure from a direct spray of dicamba as the maximum single application rate (1.0 lbs a.e./A) * 2.7 μg a.e./bee (upper boun d for contact exposures from a direct spray of 1 lb a.e./A, based on work by Kock and Weisser, 1997), the resultant RQ would be 0.03 (2.7/91) or 1 order of magnitude less than the terrestrial invertebrate LOC (0.4). Given that the actual dose that would r esult in 50% mortality is likely considerably higher than 100 μg a.e./bee, this analysis can be considered highly conservative. Although this is for only a single application of dicamba, it may be considered an appropriate estimate of exposure
from a dire ct spray as there is a 7

- day minimum interval between applications and the lifespan of a bee as a forager is 4

- 5 days (Winston, 1987). Therefore, the risk to adult honey bees posed by contact with residues of dicamba in spray drift is considered low.

A cute dietary data for non

- target insects has not been submitted to the Agency. However, a review of the EU Footprint Pesticide Properties Database reported an acute oral value for honey bees that indicates dicamba is also practically non

- toxic to non

- targ et insects on an oral exposure basis (honey bee acute oral LC 50 > 100 μg a.e./bee). If an RQ were calculated for terrestrial
invertebrates

, 2 using this non

- definitive LC 50 (and again, conservatively assuming that the highest
tested dose would result in 5 0% mortality) and determining acute dietary exposure of dicamba residues of 32.12 μg/bee/bee/day (1.0 lb a.e./A * 110 μg a.e./g {upper

- bound residue for tall grass
from T

- REX} * 0.292 g/day {pollen consumption rate}, the resultant RQ would be 0.32 (32.12/ 100) or slightly below the proposed terrestrial invertebrate LOC (0.4). Given that the actual dose that would result in 50% mortality is likely considerably higher than 100 μg a.e./bee, this analysis can be considered highly conservative.

Chronic Oral Ex posures to Adult and Larval Honey Bees

Approach The Office of Pesticide Program’s overview of the FIFRA risk assessment process (USEPA 2004) states the following:

In some instances, a core study may not be available for a particular data requirement list ed in 40 CFR 158. In this case, the risk assessment team may consider other sources of information to address the data gap.... Professional judgment is used by the risk assessment team to determine the utility of the available supplemental data for the pro posed risk assessment. (page 36 USEPA 2004)

EFED has employed, for the last decade, an acute to chronic ratio approach (USEPA 1999, Mount et al. 2003) to address data uncertainty for a variety of endpoints including survival, growth, development, and rep roduction effects from prolonged exposure. The process uses mathematical relationships observed between acute and chronic exposure effects endpoints conducted with one organism to draw inferences on the potential effects endpoints associated with longer du ration exposures in another organism, where only acute exposure effects endpoints have been measured.

3 The employed methodology for calculating an RQ for pollinators was first proposed in the 2012 Pollinator Risk Assessment Framework SAP White Paper, and subseq uently validated by the panel. The White Paper is accessible online at regulations.gov, under docket EPA

- HQ

- OPP

- 2012

- 0543

.20 Consistent with this approach, an evaluation of the invertebrate data uncertainties for dicamba focuses on the acute and chronic toxicity data for other invertebrates to determine a relative relationship between the acute toxicity endpoints and the chronic endpoints. This relationship is then examined relative to the acute toxicity data available for the dicamba equivalence (a.e.) endpoints for bees to es timate a chronic endpoint for terrestrial invertebrates. The estimated chronic/developmental endpoint is compared to available exposure information to determine if a presumption of risk is or is not supported by these lines of evidence.

Aquatic invertebr ates were selected for this approach 1) because they represent a relatively closer taxonomy to terrestrial invertebrates than would be achieved for tested vertebrate species and 2) because of a lack of a specific taxonomically

- based mechanism of action for invertebrate responses to dicamba DGA salt. Moreover, the chronic data available for aquatic invertebrates includes measures of effects on survival, reproduction, growth, and development milestones over protracted exposure windows, which are conservative ly applicable to the growth, development and survival measurement endpoints expected from acute and chronic bee larval and adult bee chronic studies.

Analysis
The available data from the cotton risk assessment for honeybees and for freshwater invertebrate s are summarized below:

Acute Daphnia magna EC 50 > 100 mg a.e./L MRID 40094602

Chronic Daphnia magna NOAEC = 42 mg a.e./L 4 MRID 48718007

Acute Honey bee contact LD 50 > 91 μg a.e./bee MRID 00036935

Acute Honey bee oral LD 50 > 100 μg a.e./bee EU Footp rint Database 5

Although the acute daphnid data are non

- definitive, a comparison of the acute and chronic endpoints, in the case of D. magna , indicates generally low acute and chronic toxicity to aquatic invertebrates with a relationship between the acute m edian lethal toxicity threshold (EC 50 ) and the chronic no observed adverse effect concentration (NOAEC) of > 2.38 (>100/42 = >2.38). Applying the minimum that this factor could be to the available honey bee median lethal endpoint would yield estimates of chronic endpoints of 38 μg a.e./bee for contact exposure and 42 μg a.e./bee for oral exposure. Although these estimates may lack conservatism since the ratio of acute to chronic toxicity in the daphnid data set may be greater than 2.38, the estimated endp oints may
still be conservative since the acute value s for bees were also not definitive ( i.e. , the highest dose
tested was below lethal levels so an actual LD 50 /LC 50 were not demonstrated), so the actual acute median lethal value is likely to be greate r and yield higher (less sensitive) estimates of chronic
effect threshold.

Following EPA’s framework for assessing pesticide risks to bees (USEPA, 2014), the acute contact estimated exposure level from dicamba DGA is 2.7 μg a.e./bee for the max imum 1 l b a. e ./A application rate. This exposure level is over an order of magnitude lower than the estimated

4 Test material was dicamba BAPMA salt

5 EU Pesticide Properties Database (PPDB), http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/213.htm21 contact

- based bee chronic NOAEC of 38 μa.e./bee. The acute dietary estimated exposure level for adult honeybees is 32.12 μg/bee/day for the maximum 1 lb a. e ./A application rate, which is also
lower than the ACR

- estimated oral exposure chronic bee endpoint of 42 μg a.e./bee. In both cases, the estimated exposure level is below the estimated chronic toxicity endpoint for survival, developmental, and repr oductive effects for honeybees under prolonged exposures, even without considering that the acute endpoints in honeybees are very conservative estimates.

Adult honeybee effects following chronic exposure effects are adequately addressed by this approach as well because the endpoint for such a test is survival under prolonged exposure and the underlying chronic exposure endpoints used in the approach were conducted at levels producing no adult invertebrate mortality. Also it is reasonable to expect that effects measures under longer term studies are a conservative surrogate for short duration exposure effects (e.g., an acute larva study measuring survival).

Because honeybee risk assessment results serve as a surrogate for assessing risks to other terrest rial invertebrates, the findings above indicate no concern for risks to the taxon overall. However, t here are uncertainties inherent in the evaluation:

1. D. magna chronic studies incorporate long exposure periods and measure survival, growth and developme nt of a juvenile crustacean life stage, which are also evaluated endpoints in acute and chronic for larval honeybee studies , but the mechanism of action may not be exactly a match for non

- crustacean arthropods such as larval insects. However, given that very similar aquatic effects extrapolations are made across a variety of aquatic invertebrate taxa, including insects, the uncertainty herein is no greater than the acceptable level of uncertainty in the aquatic invertebrate extrapolations routinely employ ed for aquatic effects characterizations.

2. Routes of exposure between aquatic organism toxicity tests and honeybee tests are not the same. Exposure media in aquatic invertebrate testing is via water, but for chronic exposure studies feeding occurs so so me oral exposure via diet is probable. Larval honeybee testing involves both dietary and dermal exposure under the laboratory testing conditions, and adult chronic honeybee studies involve dietary exposure. However, for
a chemical such as dicamba DGA sal t, once dissociated in test solution to the free acid, the exposure differences are likely not biologically significant as the uptake for the hydrophilic acid is likely diffusion across the membrane with other water soluble compounds and therefore absorpti on for either the gut or gill would be similar , though metabolic pathways may be different following uptake through the gill compared with the gut

.

The refined investigation in this document considered other lines of evidence and focused on:

1. A long stand ing EFED approach to consider the relationship between acute and chronic endpoints in the complete dataset for one organism to draw inferences on the same endpoints for another organism when data are lacking (i.e., inferring survival, growth and developmen t effects levels for terrestrial invertebrate22 developmental life stages and survival in organisms following prolonged exposure);
and

2. Comparison of resulting extrapolated invertebrate development, growth and reproduction endpoints under chronic exposure co nditions to estimated levels of

exposure.

Considering all lines of evidence, it is reasonable to conclude that risks are likely to be low to larval and adult honey bees under the conditions described in the cotton risk assessment scenarios of use
as the empirical data demonstrate low acute and chronic toxicity to other similar taxa ( i.e. aquatic invertebrates), low acute toxicity to adult honey bees and based on the ACR analysis presented here, chronic toxicity to adult and larval honey bees is also anti cipated to be low. Additionally, dicamba will be reassessed in registration review [beginning later in 2016 ]

. EPA intends to use Registration Review to facilitate submittal of additional pollinator data and is also revising the existing insect pollinator data requirements in CFR Part 158 (revision anticipated in 2017 ) to require additional data necessary to complete risk assessments consistent with the risk assessment framework. Consistent with current use of bee endpoints as a surrogate for other terrestrial invertebrates, there is sufficient information to preclude concern for direct terrestrial invertebrat e risks and any attendant indirect effects mediated through these organisms.

No data is available for the acute or chronic toxicity of dicamba’s degradate DCSA to honey bees or other pollinators (the EU footprint database does however report a 14

- D LC 50 o f > 1000 mg/kg for earthworms). However, given the low DCSA residues measured in dicamba

- tolerant seeds (max measured residue of 0.440 ppm), exposures to honey bees and other pollinators from DCSA residues in pollen and nectar of dicamba

- tolerant soybean are anticipated to be low.

As noted above for terrestrial vertebrate species, based on the available plant metabolism data for
DCSA on non

- DT plants, EFED assumed that any exposure for terrestrial invertebrates occurs as a
result of feed ing solely on DC SA in DT

- cotton plant tissues and no exposure to DCSA is expected for terrestrial invertebrates feeding off the field, even if dicamba residues should occur following spray drift or volatilization.

Terrestrial Plants

Dicamba exposure to terrestrial and s emi

- aquatic plants is estimated using the TerrPlant (version 1.2.2) model. The model generates EECs for plants residing near a use area that may be exposed via runoff and/or spray drift. The EECs are generated from one application at the maximum rate
for a particular use and compound

- specific solubility information. Only a single application is considered because it is assumed that for plants, toxic effects are likely to manifest shortly after the initial exposure and that subsequent exposures do not cont ribute to the response. Hence, the model estimates EECs based on application rate, the solubility factor, and default assumptions of drift. Parameter values for application rate, drift assumption s and incorporation depth are based upon the
use and related application method and can be found in A ppendix 3

.

The EECs and resulting RQs for terrestrial and semi

- aquatic plants for a single application of23 dicamba DGA at the maximum label rate for the proposed use on dicamba

- tolerant cotton are presented in Ta ble s 12 and 13

. RQs were exceeded for listed and non

- listed dicots due to spray
drift or in semi

- aquatic areas due to runoff and spray drift.

Table 12 . EECs for Terrestrial and Semi

- Aquatic Plants Near Dicamba Use on Dicamba

Tolerant Cotton

Crop S ingle Max. Application Rate (lbs a.e./A) EECs (lbs a.e./A) Ground Spray Total Loading to Adjacent Dry Areas (sheet runoff + drift) Total Loading to Semi

Aquatic Areas (Channel i zed runoff + drift) Drift EEC

Dicamba

Tolerant
Cotton 1.0 0.06 0.51 0.01

Table 13 . RQ values for plants in dry and semi

- aquatic areas exposed to Dicamba DGA through runoff and/or spray drift.*

Plant Type Listed Status Dry Semi

- Aquatic Spray Drift

Monocot non

- listed <0.1 0.30 <0.1

Monocot L isted <0.1 0.80 <0.1

Dicot non

- l isted 0.49 4.15 19.49

Dicot listed 0.89 7.58 38.31
*If RQ > 1.0, the LOC is exceeded, resulting in potential for risk to that plant group.

EFED’s current screening tool TerrPlant results in a RQ of 0.89 for listed species and 0.49 for non

listed speci es of dicots in dry areas

, which is less than the LOC for plants of 1.0. Risk quotients would be higher if the maximum seasonal rate (2 lb a.e./acre) were applied all at once. Moreover

, using default assumptions in AgDrift (Tier 1 ground

, low boom, fin e to medium

- coarse spray) the
LOC for both listed and non

- listed dicots (using the most sensitive species, soybean, data, Table 6 ) is exceeded at the maximum distance that the model returns (997 feet). However, the draft label contains language rest ricting applications to a specific nozzle with coarser droplet spectra and other restrictions. The implications of these restrictions on spray drift are discussed in the following
section.

The aforementioned RQ values are for the DGA salt of dicamba. For dicam ba acid, which DGA salt may dissociate to and which has more sensitive seedling emergence values, RQ values would
exceed the LOC of 1.0 for all listed and non

- listed monocots and dicots in semi

- aquatic areas and
for listed monocots and listed and non

- lis ted dicots in dry areas. It is unclear what the differences in observed toxicities of the seedling emergence and vegetative vigor studies between the DGA salt
and dicamba acid is due to. However, since the vegetative vigor endpoints for dicamba DGA to

so ybean are an order of magnitude more sensitive than any seedling emergence endpoint for dicamba acid, this is considered a minor data gap and the major route of concern for terrestrial plants is considered to be spray drift of dicamba residues following dicamba DGA applications.24 Spray Drift Analysis for Exposure to Terrestrial non

- Target Organisms

As the application rates are identical between the post

- emergent use of dicamba on tolerant

soybean and tolerant

- cotton, the following analysis that was condu cted for the concurrently issued
2 nd addendum for use on tolerant

- soybean ( USEPA, 2016b ; D426789) is also applicable for the present action on cotton.

In the first addendum to the EFED Section 3 risk assessment for dicamba DGA salt for use on
dicamba

- tolerant soybeans (D404138, 5/20/14), EFED estimated that a realistic distance from the application site to where no effects are observed to sensitive plants (based on the NOAEC for the most sensitive apical endpoint of plant height for the most sensitive tested species, non

- dicamba tolerant soybeans) ranged from 1 00 to 175 feet (for the 0.5 lb a.e ./A tolerant

- soybean post

emergent application rate) or approximately double that for the pre

- emergent max application rate
of 1.0 lb/A . However, based on a weight of evidence approach and refined AgDrift modeling for coarser droplet spectra (coarse to ultra

- course droplet distribution), EFED refined this distance to 124 feet (rounded up to 125 feet) or to 107 feet if label language were to restrict the droplet size to solely ex tra

- coarse and ultra

- coarse droplet sizes).

EFED further refined this analysis after receiving more information including a spray drift deposition study submitted by BASF (MRID 49067704). In light of this information, Monsanto proposed that the spray dri ft buffer distance be reduced to 70 feet for M1691 Herbicide using the TTI 11004 nozzle at application spray pressures ≤ 63 psi. EFED’s subsequent analysis for submitted field trial data (presented below), however, indicates that a larger buffer may be

ne cessary in order to limit potential effects to sensitive plants to the sprayed field. Linking this data to our previous modeling efforts and employing a weight of evidence approach, EFED proposes that the label should be modified to include language to ma intain a 100 to 110 foot downwind buffer when applying at the 0.5 lbs a.e./A application rate. The July 2015 amended labels subsequently submitted by Monsanto included a 110 foot buffer and 220 foot
buffer for 0.5 and 1 .0 lbs a.e./A application rates, respectively.

Field Trial Data Discussion

Subsequent to EPA’s 5/20/2014 addendum, Monsanto presented information from academic field research that had not previously been submitted to the Agency for review. EPA requested data
from these field trials and Monsanto submitted the raw data (MRID 49612701 pg. 51) on 4/13/2015 along with a response document (MRID 49570501 pg. 1). Monsanto’s response document
included an analysis that the 70 foot buffer would be protective of the no

- effect distance for
sensitive plants ( the “no

- effect” distance is based on the most sensitive NOAEC for the apical endpoint of plant height for the most sensitive tested species, non

- dicamba tolerant soybeans) for 7 of the 9 submitted trials and a proposed rationale for why it may not have been protective in the remaining 2 trials. The response document also included Monsanto’s statement that the field trial data are not suitable for use in EPA’s regulatory decision

- making process, but overall support the
then

- proposed 70 foot buffer.25 While EFED agrees that the field trial data are generally not suitable for regulatory decision

making, we believe that they demonstrate additional uncertainty that the previously proposed 70 foot buffer would be sufficient to prevent potential effects to non

- target plants that are off the field. In an attempt to conduct a quantitative evaluation of the field trial data, EFED considered that the data could reasonably represent a dose

- response effect, with higher treatment doses expected to be
closer to th e application site. In this context, the distances farthest from the application site were considered to be likely to have little to no dicamba residues and loosely were considered controls. EFED then considered that plant heights and yield (similar to o ur apical endpoints of plant height and biomass from the standard vegetative vigor plant ecotoxicity tests) at the closer distances ( i.e. treatment groups) could be compared to those of plants at the “control” distances using statistical hypothesis tests, similar to our standard statistical methodologies for data evaluation of ecotoxicity tests. In an effort to streamline the data analysis process, EFED used standard t

- tests in Excel to conduct the analysis.

This statistical analysis indicated that a maj ority (5/9) of the field tri als provided evidence that the proposed 70 foot buffer would not be sufficient to keep any effects to sensitive plants’ apical endpoints contained to the field. Three of the nine trial sites had significant inhibitions compare d to the “control groups” at distances greater than EFED’s refined buffer of 125 feet, though EFED notes Monsanto’s rationale for the greater distances in two of those sites (Monmouth, IL and Haubstadt, IN) might be due to applications not conforming to th e currently proposed label
restrictions for M

- 1691 Herbicide. The maximum “no effect” spray drift distance that EFED determined for the remaining site (Rower, AR) was 147.5 feet.

Since these field trials involved no true controls and residue analysis was not conducted to confirm the lack of residues in the farthest plants, the magnitude of an effect seen between “treatment” groups and true control plants might be higher than what this analysis indicates. These field trials
were all conducted at the 0.5 lb s a .e ./A (maximum single post

- emergent application rate) and all were conducted using the TTI11004 nozzle in accordance with the label directions. The operating pressures varied across the sites from 30 psi to 50 psi (other than for the Haubstadt trial si te, for which nozzle pressures were not recorded), which is less than the labeled maximum operating pressure of 63 psi. Higher operating pressures than used in these field trials (but within the proposed labeled directions for use), may result in an incre ased proportion of finer spray droplets and consequently result in effects at distances greater than observed in these field trials. The specific process, results and conclusions that EFED used in evaluating Monsanto’s submitted field
trial data and relat ing it as an additional line of evidence in determining an appropriate buffer that would result in no adverse effects to EPA’s apical endpoints for terrestrial plants (the most sensitive taxa to the herbicide dicamba), is discussed immediately below.

Detai ls of EFED’s Process to Determine a “No Effect” Spray Drift Buffer from the Available Field Trial (MRID 49612701 pg. 51 ) Data:

Transects (at each site or for each swath, where multiple swaths were tested) were combined to determine mean soybean (non dicam ba

- tolerant) plant heights (14 & 28 DAT) or yields at set
distances. The farthest two distances for which plant height or yield data were recorded were considered “controls,” though there are considerable uncertainties to this approach. Specifically,26 no true controls were used, no residue analysis was conducted to confirm that these plants were not exposed to dicamba (or other chemical) residues, data were only recorded when there was at least 5% visual response (which could have been due to a number of f actors including potential dicamba residues) and for many of these “controls” the height/yield endpoint may not have been recorded in all transects, resulting in a lower sample size (n) for controls and therefore a decreased power in the
statistical t

- test

. All analyses were conducted in MS Excel. Means for each distance towards the sprayer were compared to the “control” means to determine the percent inhibition at each distance. T

- tests (1

- tailed, assumed equal variances unless an F

- test {p<0.05} showe d unequal variances) were conducted to compare the endpoints of the treatment distances to the controls. Since these were field tests and had considerable uncertainties surrounding the controls, EFED considered significance at the (α=) 0.1 level which inc reases the conservatism of the analysis. The buffer for a “no effect” distance at each site was considered the first distance greater than a distance which had a significant decrease compared to the control group. For example, at the Brooksville, MS site , the furthest distance which exhibited a significant decrease (p<0.10) in height at 28 DAT compared to the control group was 86.25 feet. The next highest distance at which soybean heights were measured was 96.25 feet (not significant, p=0.19), which there fore was considered the “no effect”
distance buffer for that site.

Results of the Analysis of the Field Trial ( MRID 49612701 ) Data

After reviewing this field trial data, EFED made the following findings. Of the nine field trials discussed above, a majorit y ( five ) provide evidence that a 70 foot buffer may not be sufficient, and four provide evidence that a 100 foot buffer may not be sufficient ( Table 1 ). With a buffer distance of 125 feet for a 0.5 lb a.i./A application rate, 3 sites (33%) would provide e vidence that a larger buffer might be necessary, with Monsanto stating (and subsequently providing information) that two of these (Monmouth and Haubstadt) may not have followed the currently proposed label by either using a different formulation or applyin g when wind speed was lower than required by the current proposed draft label.27 Table 1 4 . Distance (in feet) from Site of Application to a "No Effect" *

Site Height (ft.)
14 DAT Height (ft.)
28 DAT Yield (ft.) Comments

Brooks ville,
MS 46.25 96.25 66.25

Rower, AR 7.9 20.6 248.7** 14 DAT “controls” had only n=2. 28 DAT controls
had n=3. * *Note , for yield, after the 12% inhibition at 223.4’, no treatment group was significantly (p<0.1) inhibited compared to controls (inhibiti ons ranged from 1.03

— 23.75% after this). The higher inhibitions were not significant due to the use of the nonequal variance t

- test, but would have been had we assumed equal variances). Therefore, using best professional judgment informed by the data and t

test results , EFED has reduced the no effect distance for this endpoint to 147.5’ , after which all inhibitions at shorter distances were > 10% (other than 1.1% inhibition at 7.9 feet). W. Lafeyette,
IN 66.25 26.25 No Data 14 DAT “controls” had n=3, 28 DAT “controls”
had n=2 Scott, MS 26.25 26.25 66.25 Jackson, TN 16.25 16.25 16.25 Yield “controls” had n=4. Kirkwood, IL 116.25 116.25 16.25

Monmouth,
IL Swath 1 74.2 137.8 0 14 DAT controls had n=4, 28 DAT controls had n=3, Yield controls had n=3
M onmouth,
IL Swath 2 53 95.4 254.4 14 DAT controls had n=3, 28 DAT controls had n=2, Yield controls had n=2 Haubstadt,
IN Swath 1 30 80 10 Swath 1 only took measurements to a maximum of 100 feet. 14 DAT controls had n=5, 28 DAT
controls had n=3
Haubstadt

, IN Swath 2 40 80 150 14 DAT controls had n=3, 28 DAT controls had n=3, Yield controls had n=2 Gilbert, IA

Swath 1 N/A N/A N/A This swath was not evaluated as no field measurements were taken past 30 feet. Gilbert, IA

Swath 2 35 15 5 14 & 28 DAT and Yi eld controls had n=4. For yield, no distance had lower mean yield compared
to controls. * Distance based on Plant Height after 14 and 28 days after treatment (DAT) and Yield (α = 0.10). No effect” indicates no reduction in plant height or biomass relative to controls. In controls, the sample size (n) is considered 6 (or 10 for Brooksville, MS and Scott, MS trial sites) unless otherwise noted in the comments section where fewer controls may affect the power of the test.28 Conclusions for the field trial data and weight of evidence approach for spray drift

After reviewing the field trial dat a submitted to EPA, EFED finds that there is considerable uncertainty around the use of a 70 foot in

- field buffer with the intent to keep any adverse effects (related to our apical endpoints of plant height and biomass) on the field , as the majority of the sites appeared to have effects on plant height at distances past this . Though the quality of the data is not suitable for the purpose of establishing an quantitative buffer distance (especially as the lack of true controls may mean that the magnitude of effects to true control plants could be greater than indicated here), EFED believes this data provides a line of evidence that an in

- field buffer greater than 70 feet is warranted to ensure protection of listed species, such as that determined in our previ ous risk assessment addendum for soybeans (D404138, 5/20/14) which used a refined modeling approach extracting out the coarse, extra

- coarse and ultra

- coarse droplet spectra to determine an average 124 foot buffer (rounded up to 125 feet) or solely the extr a - coarse and
ultra

- coarse droplet spectra for an estimated average distance of 107 feet (rounded up to 110 feet) for a 0.5 lbs a.i./A application. The draft label only supports the use of one nozzle ( Tee Jet®
TTI11004 ) with a maximum operating pressure o f 63 psi which restricts droplet spectra to ultra

coarse and extremely coarse

. Using a weight of evidence approach ( covering the refined modeling analysis conducted in the previous risk assessment addendum, the spray drift deposition study submitted by BASF (MRID 49067704) and the submitted field trial data discussed here), EFED concluded that the label should be modified to include language to maintain a 100 to 110 foot downwind buffer when applying at the 0.5 lbs a.i./A application rate with nozzles and op erating pressures that at a minimum restrict droplet spectra to ultra

- coarse and extremely coarse

. The July 2015 amended labels subsequently submitted by Monsanto included a 110 foot buffer and 220 foot
buffer for 0.5 and 1 .0 lbs a.e./A application rate s, respectively

. Further data that may help refine this estimate w ould be field trial data with actual controls (and/or residue analysis to indicate a lack of dicamba or other herbicide treatments), larger control sample sizes and transect replication, field measurements provided regardless of whether plant visual

respon se (damage) was observed or not, a greater number of swaths at each trial site (reflective of typical practices in soybean agriculture) and using the maximum labeled nozzle operating pressure.

Vapor Analysis for Drift Exposure to non

- Target Organisms

Aft er reviewing data submitted to EPA relating to the volatility of dicamba, EFED had concerns regarding the volatility of dicamba, and possible post

- application, vapor

- phase off

- site transport that might damage non

- target plants. Monsanto responded to these concerns with a submission (MRID 49612701 pg. 143) that acknowledged the long

- recognized volatility of dicamba and
described measurements of the volatilization in the different formulations.

The information submitted to address EFED’s concerns was hel pful, but the submission did not include enough detail to verify the measurements in the studies. EFED determined that it would be useful also to perform volatility experiments under varied conditions of temperature and relative humidity, as these factors seem to be important in field conditions.29 The registrant has agreed to place directional, in

- field spray drift buffers of 110 feet for the 0.5 pound per acre application rate and 2 20 feet for the 1.0 pound per acre application rate. One open
literatu re study (Egan and Mortensen 2012), directly addresses the potential for volatilization and transport of dicamba, and the potential for damage to the most sensitive tested species, soybean (non dicamba

- tolerant ). Based on damage assessments of n on dicamba

- tolerant soybean plants placed near treated fields after spray drift from a 0.5 lb/A DGA salt application had dissipated, the
authors estimated the exposure at distance by correlation to known dose

- damage correlations. They
estimated that the 9 5% upper bound vapor exposure would drop below the soybean NOAEC at approximately a distance of 25 meters (82 feet). This is well within the 110

- foot spray drift buffer proposed for the 0.5

- lb/A rate. Thus, based on at least one study, this buffer dis tance should be adequate to protect against volatilization exposure for EPA’s apical endpoints of plant height and yield. However consideration should be made as to whether this buffer distance should be applied on all sides of the field, rather than the c urrently labeled uni

- directional buffer according to wind
direction.

The incident described by MDA in the following section (EIIS incident number I026579

- 001 ) provides limited information that the proposed 110 to 220

- foot spray drift buffers would not be adequate to limit off

- site plant damage due to post

- application volatilization. However, since the incident only qualitatively describes visual damage, while the buffer is intended to be protective of apical endpoints of height and yield, this remains an uncertainty , and would benefit from additional field trial data under varied conditions of temperature and relative humidity. Based on the best available data for dicamba residues from vapor drift compared to effects on apical endpoints, EFED
believes t hat a 110 foot buffer for the 0.5 lb ae/A application rate should be adequate to protect against effects on non

- target plants from volatilization of dicamba residues. This analysis similarly suggests that a 220

- foot buffer is protective for the 1.0 lb ae/ A application rate , though this may be overly conservative since the 1.0 lb ae/A rate is for pre

- emergent applications that may be applied under conditions less conducive to vapor drift ( e.g. cooler temperatures )

Incident Data

A preliminary review on January 20, 2016 , of the Ecological Incident Information System (EIIS, version 2.1), which is maintained by the Agency’s Office of Pesticide Programs, and the Avian Monitoring Information System (AIMS), which is maintained by the American Bird Conservancy,
indicates a total of 11 reported ecological incidents associated with the use of DGA salt. This total excludes incidents classified as ‘unlikely’ or ‘unrelated’ and only includes those incidents with certainty categories of ‘possible’, ‘probable’, and ‘hi ghly probable’ (for EIIS) and ‘possible’, ‘probable’, ‘likely’, ‘highly likely’ and ‘certai n’ (for AIMS ). Incidents classified as ‘unlikely’ the result of or ‘unrelated’ to DGA salt will not be included in this ecological risk assessment. The
EIIS databa se identifies numerous additional ecological incidents with the dicamba acid (70 incidents) and various dicamba salts (104 incidents across all salts). EFED investigated whether any of the incidents in the database were associated with dicamba use on dicam ba

- tolerant crops. Four of the 11 incidents in the EIIS database involving the DGA salt involved applications to
dicamba

- tolerant soybean and resulting damage to non

- dicamba tolerant crops. No incidents are currently reported in the EIIS database for inci dents stemming from the use on DT

- cotton, however recent information submitted by Missouri and Arkansas regulatory agencies (discussed below)30 include incidents associated with the use of dicamba on DT

- cotton that occurred in 2015. Details
on the recent in cidents stemming from use on DT

- soybean and cotton are provided below

.

In addition to the review of the available incident databases , EFED is aware of other recent incident
information where non

- dicamba tolerant plants were damaged following applications of dicamba
DGA salt to DT

- soybeans or DT

- cotton. This recent incident information, su bmitted by Monsanto and state regulatory agencies in Missouri and Arkansas, is discussed below.

Recent Incident Information Provided by Monsanto and MO and AR Regulatory Agencies

Incident Reports Submitted by Monsanto (2012

- 2014)

Monsanto provided inf ormation for 73 incidents involving the M1691 formulation from 2012 to 2014. In their response document (MRID 49612701 pg. 68 ), Monsanto notes that observations were solely qualitative visual estimates and that no measurements of apical endpoints such as plant height or yield were taken. Monsanto further noted that the incidents related either to seed production activities or to activities performed as part of the product development process relating to product stewardship. They stated that current pro posed label requirements were not in place in 2012, that all of these incidents either did not follow all of the current draft label requirements (including tank mixtures with additional pesticide active ingredients such as glyphosate, nozzle type, w ind

- speed, wind direction, spray volume, etc.) or they were a result of other factors ( e.g. burndown application, heavy rainfall, equipment contamination, spillage, etc.) and that the percentage of incidents as a function of the number of applications made has decreased in each subsequent year since 2012.

EFED has conducted an initial review of these incidents and generally agrees with Monsanto that the incidents resulted from applications not in accordance with currently proposed draft label language or were attributed to other (non

- dicamba) factors. However, four incidents (Inquiries 19, 20, 24, and 30) from 2014 lacked sufficient information in the report (such as on tank mixture, application rates, nozzles, wind direction & speed, equipment speed, buffer distance, spray volume & pressure or boom height) to determine whether their occurrence followed applications that were in accordance with the current proposed draft label requirements. Although , as Monsanto notes,
much of this data arises from se ed production activities or activities related to the product development process and were not generated for purposes of risk assessment, EFED does not discount that they could be suggestive of potential incidents in the field and they could provide
useful information to that end

.

EFED also acknowledges that the incident observations are qualitative measures of visual injury ( e.g. leaf spotting or curling) . Nonetheless, the information presented in these incidents may be
useful if future labels incorpor ate changes such as potential tank mixes with additional active ingredients or additional nozzle types

, since some of these incidents include information on tank mixes and nozzle types which would be relevant in the case where those changes are made to the
label.31 Missouri and Arkansas Case files

The Missouri Department of Agriculture (MDA) has submitted information for incidents occurring from 2013 to 2015 and the Arkansas Plant Board (APB) has submitted information for incidents occurring in 2015, rega rding observations of dicamba

- type damage to non

- tolerant plants following either preemergence or postemegence applications to dicamba

- tolerant (DT) soybeans or cotton. Similar to the incidents reported by Monsanto for 2012

- 2014, all of the incidents were qualitative visual estimates and no observations or measurements of apical endpoints such as plant height or yield were taken.

2013

- 2014 Incidents

MDA has notified EPA of two incidents following potential dicamba applications that occurred in
2013 and 2014. In 2013, dicamba

- type damage was observed in a non

- DT soybean field (MO Case File #81513M00701, EIIS Incident report number I026579

- 001). The only dicamba application in the area was reported to be a Clarity herbicide application on DT

- soybeans 2,8 00 feet from the damaged field. Pesticides were applied using XR T

- Jet 11004 nozzle, which is the same nozzle proposed for the new dicamba uses on DT cotton. The applicator was informed of this incident in January 2014. Dicamba residues were found in one foliage sample taken from the affected field at 42 μg/kg

. In the other two taken samples, dicamba residues were not detected (limit of detection not reported, but a limit of quantification of 3.8 μg/kg). The case file submitted to the agency did not orig inally determine the cause of the dicamba damage. In subsequent communication with the Agency (2015 letter from D. Slade, MDA to Grant Rowland, EPA), MDA concluded that the application of Clarity herbicide was not transported to the affected site by spray drift, but by later
volatilization.

In their response document (MRID 49612701 pg. 1, submitted prior to MDA’s December, 2015 letter), Monsanto noted that it has reviewed the complete incident report from the Missouri Department of Agriculture (MRID 496 12701 pg. 75). Monsanto stated that the report indicated that 1) there was potential the crop visual injury response was observed prior to the dicamba application, 2) MO Department of Agriculture did not come to a definitive conclusion on the primary caus e of the incident and 3) other plausible explanations were not investigated, such as temperature inversion, alternative sources of dicamba, such as leaking equipment or damage from other herbicides. Therefore, Monsanto concluded that the incident did not provide evidence that the observed plant response was a result of exposure to vapor drift of dicamba residues. Monsanto also included this incident in their description of the 73 incidents from 2012

- 2014 discussed previously in this section and no ted that this incident would not comply with the current proposed label requirements as M1691 was tank mixed with glyphosate and other adjuvants.

EPA notes that MDA has now completed their investigation of this incident, measured residues indicating the presence of dicamba residues on the affected site, concluded that dicamba volatilization rather than drift was the likely cause of the damage and initiated enforcement action against the applicator for allowing the product to move from the target field. T he climatic conditions at the time of application were slightly outside of the range of conditions from the available laboratory studies on dicamba DGA salt’s volatility. Given that effects to EPA’s apical endpoints of plant height and biomass were not mea sured, there is uncertainty regarding whether32 this incident indicates that volatilization following dicamba applications may result in impacts to apical endpoints beyond the proposed spray drift buffer of 110 feet for a 0.5 lb/A application. However, base d on the available data, a volatilization buffer equal to the spray drift buffers, and extending in all directions form the treated field, is justified

. The current proposed labels only apply a unidirectional spray drift buffer in the direction wind is blowing.

MDA also notified EPA of an incident in 2014 (MO Case File #072214MO0701) where “dicamba type” damage was observed on a non

- DT cotton field where the only nearby dicamba application would have been a Clarity herbicide application on DT

- soybean s, 2.2 miles from the affected site. As with the other incidents, the provided information only indicated observations of visual injury and not effects to apical en dpoints such as plant height and yield. Residue samples taken from the
affected site faile d to detect dicamba residues. It is unclear whether this incident was also included
in Monsanto’s submitted information on the 73 incidents from 2012

- 2014. With the current information and due to the lack of identified dicamba residues, it is uncertain wh ether the damage observed in the incident was a result of dicamba applications or due to some other unidentified cause. If the observed damage was caused by dicamba, than given the large distance between the affected site and the nearest known dicamba app lication, it would likely have been a result of volatilization, rather than spray drift.

2015 Incidents

Missouri and Arkansas recently submitted to EPA a total of 15 incidents in 2015 that might be attributed to dicamba use (12 in Arkansas and 3 in Mis souri) on cotton . The information indicates that these incidents resulted from 6 separate instances of applications of dicamba, with 8 of the incidents (7 from Arkansas and 1 from Missouri) being a result of a single instance of a post

emergent dicamba ap plication to DT

- cotton of Strut herbicide (active ingredient Dicamba DGA),
tank

- mixed with glyphosate and applied at two times the labeled rate for the proposed Clarity/M1691 post

- emergent use. Visual observations of plant damage extended to 1320 feet (1/ 4 mile) from the application site, but the provided incident information did not provide sufficient details to ascertain damage to EPA’s apical endpoints of plant height or yield. The remaining incidents were pre

- emergent applications of dicamba or at thi s time remain uncertain as to whether any application of dicamba was made. Results of residue analyses for these incidents are currently
not available.

Conclusions Regarding Incident Information 2012

— 2015

Conclusions Regarding Incident Information 2012

— 2 015

For the purposes of the registration of dicamba on dicamba

- tolerant soybean and cotton crops, the incident information available at this time indicates that the vast majority of incidents occurred following applications that were not made according to the current draft label requirements. Label requirements that differ from the draft label being evaluated here include the restriction against tank mixes with other active ingredients and adjuvants, higher application rates, and applications with
differe nt nozzle types and climatic conditions than permitted according to the draft label. Quantitative measurements of yield loss or decreased plant height were not made in any of the incident descriptions. Currently, EPA has no methodology for relating qualit ative estimates of33 visual damage to quantitative effects to apical endpoints.

Most of these incidents were likely caused by spray drift off the field following the application. The only incident where volatility of dicamba residues has been concluded to be the cause of the incident by a regulatory agency (MDA for MO Case File #81513M00701, EIIS Incident report
number I026579

- 001) was an incident where the application was also made as a tank mix of glyphosate, additional adjuvants and dicamba. However, E FED believes that this difference from the draft label is unlikely to have impacted the ability of dicamba residues to volatilize as the different active ingredients and adjuvants are generally presumed to have disassociated from each other by the time any volatilization would occur. Rather, the volatilization may have been more impacted by the climatic conditions (temperature and humid ity) in the days following the application which fall outside of the range of submitted laboratory conditions f or which EPA has
data.

Runoff

The Agency considers spray drift exposure to be the principal risk issue associated with the proposed label use of dicamba DGA s alt, owing to a variety of lines of evidence, including past experience with other dicamba formulations and associated spray drift incident reporting. However, in the following paragraphs the Agency provides an explicit consideration of the runoff
risks a nd effects of proposed mitigation to limit off

- site runoff in listed species effects
determination.

An important component of the model used for terrestrial risk assessment (TerrPlant) is the assumption that the mass of pesticide running off the trea ted field is directly related to the pesticide’s solubility in water. In the case of dicamba DGA salt, the dissociated salt yields highly soluble dicamba acid. The TerrPlant model assumes that the high solubility of the acid results in a
runoff mass of 5 percent of the field

- applied mass. The model also includes an assumption that the

non

- target plant receptors in the runoff zone are exposed to a single pulse of the total mass. The TerrPlant model does not account for any pesticide degradation or partitio ning, nor does it account for the temporal aspects of runoff associated with meteorological events (i.e., runoff follows precipitation events that exceed field capacity of the soil). The fate characters tics of dicamba
indicate that it is not environmentally persistent. Therefore, TerrPlant is likely providing a highly conservative estimate of runoff loading at any given time because the processes of degradation and partitioning combined with the stochastic nature of runoff are important limiting factors for
dicamba.

A refined characterization of potential pesticide runoff is routinely considered in aquatic system exposure modeling through the use of the Surface Water Concentration Calculator (S WCC). EFED has turned to this model to ascertain the extent to which explicit consideration of degradation, partitioning, and stochastic runoff events would lead to a more mechanistically appropriate runoff exposure estimate than is possible using TerrPlan t. Using the SWCC Missouri cotton scenario run for the cotton risk assessment (D404823) and assuming one application of dicamba DGA at 1 pound per acre, followed by two half

- pound applications at seven

- day intervals, EFED has determined that the total year ly mass of dicamba in runoff from a 10 hectare (24.7 acre) treated field is ~0.055% of the applied mass (see Appendix 4 for calculations). Using these assumptions in34 TerrPlant (total 2 lb ae/A application and a 0.055% runoff fraction), and the most sensiti ve endpoint of 0.000261 for the NOAEC for soybeans, the maximum RQ is less than the LOC of 1.0 by a factor of at least 2 (RQs range from <0.1 to 0.48, see Appendix 4 ).

Combining the predictions of SWCC modeling and the expectation that much of the off

- sit e plant community will not experience foliar contact with dicamba DGA in runoff sheet flow, EFED concludes that all available lines of evidence support a “no effects” determination for runoff exposure for off

- field listed plants for the proposed labeled us e of dicamba DGA.

Herbicide Interactions (Synergism )

Mixtures of herbicides, such as those applied in tank mixtures, may cause synergistic, antagonistic,
or additive effect in non

- target plants, compared to the effects of the individual herbicides. The patent and literature studies cited below indicate that combinations of dicamba and glyphosate may cause effects that range from synergistic to antagonistic, depending on the plants tested and the
doses used.

In the case of dicamba and glyphosate, a pate nt (Satchivi and Wright 2011) filed by DowAgrosciences LLC claimed synergistic effects in Chenopodium album (common lambsquarters) and Commelina benghalensis (dayflower), but no synergism in Conyza canadensis (Horseweed/marestail).

Flint and Barrett (1989 a) studied the combined effects of dicamba and glyphosate on field bindweed ( Convolvulus arvensis ) and found synergistic inhibitory effects on the root system. Flint and Barrett (1989b) also studied interactions between dicamba and glyphosate in Johnsongra ss ( Sorghum halepense ). They found antagonistic effects of dicamba on shoot and root fresh weights, compared to lower rates of glyphosate alone.

Kelley et al. (2005) studied the interactions of dicamba with four herbicides, including glyphosate,
in non

- G MO soybeans. Dicamba was not found to be synergistic with glyphosate considering plant injury and yield loss as endpoints.

Olszyk et al. (2015) tested the interaction of dicamba and glyphosate (at three different rates) in eight plant species, including big bluestem ( Andropogon gerardii ), Milkweed ( Ascelepiassyriaca spp.), purple node joe pye weed ( Eutrochium purpureum ), soybean ( Glycine max ), evening primrose ( Oenothera biennis ), slender knodding smartweed ( Polygonum lapathifolium ), Canada goldenrod ( Sol idago canadensis ), and purple top tridens ( Tridens flavus ). Generally, antagonistic effects were found in plant growth endpoints and the study authors concluded that no combination of dicamba with differing glyphosate rates produced a synergistic response for any species.

The current draft label for dicamba use on tolerant soybean and cotton plants specifies that tank mixes may only be used for products that have been tested and found not to have unreasonable adverse effects on the spray drift propertie s of M1691 Herbicide. EFED believes that guideline laboratory studies of effects to terrestrial plants should be required for any product or tank mixture combining dicamba and other active ingredients to assess risks associated with any tank mixture for
use on dicamba

- tolerant soybeans or cotton. Testing of such products should include the standard35 suite of tested species from the already submitted dicamba and tank mixed active ingredien t vegetative vigor studies as well as those that the open literature and patent data indicate potential
for synergistic effects

.

FEDERALLY

- LISTED SPECIES

This assessment does not include effects determinations for any identified federally

- listed endangered and threatened species (listed species) . A more in

- depth listed species

- specifi c effects determination will be conducted using the information from this analysis. The i dentified potential risks to listed species from th is screening

- level risk assessment are summarized in Table 1 4

.

TABLE 14 . Listed Species Risks A ssociated with Potential Screening Level Direct or Indirect Effects Due to the Proposed Applications of Dicamba on Dicamba

- Tolerant Cotton

.

LISTED TAXON DIRECT EFFECTS INDIRECT EFFECTS

Terrestrial and semi

- aquatic plants

– monocots No 1 Yes 2

Terrestrial and semi

- aquatic plants

– dicots Yes Yes 2

Insects No Yes 2

Birds Yes (Acute) Yes 2

Terrestrial phase amphibians Yes (Acute) Yes 2

Reptiles Yes (Acute) Yes 2

Mammals Yes (Chronic) Yes 2

Aquatic plants Yes (Non

- vascular) Yes 2

Freshwater fish No Yes 2

Aqua tic phase amphibians No Yes 2

Freshwater crustaceans No Yes 2

Mollusks No Yes 2

Marine/estuarine fish No Yes 2

Marine/estuarine crustaceans N o Yes 2

1 Listed species of monocots RQ values did not indicate risk from DGA salt, but risk was indicated for dicam ba acid.36 DGA salt rapidly disassociate s into dicamba acid

. 2 The listed chronic LOC was exceeded for mammals , birds and dicot species of plants . Therefore, the potential for adverse effects to those species that rely on a specific animal species

, multip le animal species

, or dicot plant species cannot be precluded in the screening

- level assessment . Indirect effects may include general habitat modification, loss of pollinators/seed dispersers, and food supply disruption.

At this time, no federally

- liste d taxa can be excluded from the potential for direct and/or indirect effects from the proposed new uses of dicamba, since there is a potential for indirect effects to taxa that might rely on plants, birds, and/or mammals for some stage of their life

- cycle. Further refinement for the endangered species assessment is provided in a separate document that includes species

- specific effects determinations

.

UNCERTAINTIES

Based on the usage of other herbicides associated with genetically modified crops that a re tolerant to a specific herbicide ( e.g., glyphosate

- tolerant soybean), the use of dicamba on cotton as a result of this expanded new use [lbs acid equivalent (a.e.) applied per year] could potentially increase

w hen compared to historical dicamba usage da ta. This is due to a variety of factors including the fact that once a tolerant crop is grown in a particular area, the use of the tolerant crop is often adopted by neighbors (to minimize the potential risk from spray drift). Additionally, dicamba use

on tolerant cotton is predicted to increase given the recent resistance issues identified in glyphosate

tolerant crops (J. Tooker, D. Mortensen, and F. Egan, pers. comm., Nov. 2010; Mortensen 2010). Although EFED does not typically address specific concerns related to the increased usage of a chemical, the potential for ecological risks likely increases with increased usage. BEAD should be consulted on the potential for increase d us age

.

Additionally, applications during a warmer time ( i.e ., post

- emergenc e as would be included in the proposed new use ) may increase off

- site transport (via volatility) during a time when many plants have leafed out (J. Tooker, D. Mortensen, and F. Egan, pers. comm., Nov. 2010; Mortensen 2010). Therefore, a post

- emergence app lication may increase the likelihood of effects to non

- target plants through habitat loss. This could indirectly affect those organisms which rely on those plants, including pollinators, th ough this is uncertain and requires additional evaluation. Provi ded the in

field buffer restricts spray drift/volatility of dicamba residues to the field, effects to non

- target plants should be limited

. For endangered species determinations (assessed in separate documents published concurrently with this risk assessme nt ), e ffects to listed species critical habitat from the
use of dicamba on dicamba

- tolerant cotton will be considered.

It is also possible that the proposed new use of dicamba on dicamba

- tolerant cotton may increase
the occurrence of weeds that are resi stant to dicamba. The occurrence of weed resistance to glyphosate has increased significantly since the adoption of transgenic glyphosate

- resistant crops (Powles, 2008). Prior to development of glyphosate

- resistant crops, there were no known cases of

evo lved glyphosate

- resistant weeds (Dyer, 1994). There exists potential that a similar pattern of rapidly evolving weed resistance to dicamba could occur where transgenic dicamba

- resistant crops
are used. Weed resistance issues are being considered by the Bi ological and Economic Analysis Division (BEAD) through product labeling and stewardship efforts.37 The formation and persistence of dicamba’s metabolite, DCSA , is an uncertainty that impacts the
terrestrial animal risk assessment. Plant metabolism studies that evaluate DCSA residues in DT

cotton plant tissues over time would decrease this uncertainty. However, the b est available data
indicate that residues of DCSA in DT

- cotton plants are unlikely to result in risk to terrestrial
animals.

References :

Al

- Khatib, K. and A. Tamhane. 1999. Pea ( Pisum sativum ) response to low rates of selected

foliar

- and soil

- applied sulfonyl

- urea herbicides. Weed Technology Vol. 13: 753

- 758.

Auch, D.E., and W.E. Arnold. 1978. Dicamba use and injury on soybeans ( Gl ycine max ) in South

Dakota. Weed Sci ence Vol. 25: 471

- 475.

Dyer, W.E. 1994. Resistance to glyphosate. In Herbicide Resistance in Plants: Biology and Biochemistry. Ed. By Powles, S.B. and J.A. Holturn. CRC Lewis Publishers, New York, NY.

229

— 241.

Ever itt, J.D. and J.W. Keeling (2009) Cotton Growth and Yield Response to Simulated 2,4

- D and Dicamba Drift. Weed Technology: Vol. 23, No. 4, pp. 503

- 506.

Hamilton, K.C. and H.F. Arle. 1979. Response of Cotton ( Gossypium hirsutum ) to Dicamba.

Weed Science. V ol. 27(6): 604

- 607.

Kelley, K.B., L.M. Wax, A.G. Hager, and D.E. Riechers. 2005. Soybean response to plant growth regulator herbicides is affected by other postemergence herbicides. Weed Science: Vol. 53(1):

101

- 112.

Marple, M.E., K. Al

- Khatib, and D .E. Peterson. 2008. Cotton injury and yield as affected by simulated drift of 2,4

- D and dicamba. Weed Technology. Vol. 22: 609

- 614.

Mortensen , D.A. 2010 . Statement to the House, Domestic Policy Subcommittee of the Oversight

and Government Reform Commi ttee. Are 'Superweeds' an Outgrowth of USDA Biotech Policy? Hearing, July 28, 2010. Available at : http://oversight.house.gov/index.php?option=com_cont ent&view=article&id=921%3A07

- 28

- 2010 ; Accessed: 03/02/2011.

Powles, S.B. 2008. Evolved glyphosate

- resistant weeds around the world: lessons to be learnt. Pest Manag Sci. 64: 360

- 365.

Satchivi, N and Wright, T, 2011. Synergistic herbicidal composition containing a dicamba

der ivative and a glyphosate derivative. World Intellectual Property Organization publication no. WO 2011/140020 A2., 10 November 2011.38 Teske, M.E., Bird, S.L., Esterly, D.M., Ray, S.L., Perry, S.G. 2001 . A User’s Guide for AgDRIFT ® 2.01: A Tiered Approach for the Assessment of Spray Drift of Pesticides ( Regulatory Version ). Spray Drift Task Force, Macon, MS. CDI Report No. 01

- 02.

USEPA, 1983. Dicamba Registration Standard Memorandum. Health Effects Di vision. Office of Pesticide Programs . Washington, D.C. August 12, 1983.

USEPA, 1984. PP#4G3061 Dicamba on Various Crops (Accession Numbers: 071410, 072411, 072412, 072413, 072414, 072415, 072416). Evaluation of Analytical Methods and Residue Data.
He alth Effects Division, Office of Pesticide Programs. Washington, D.C. August 30, 1984.

U.S. Environmental Protection Agency (USEPA). 2005 a . EFED Reregistration Chapter for
Dicamba/Dicamba Salts. Environmental Fate and Effects Division. Office of Pesti cide Programs. August 31, 2005 (DP Barcode 317696).

USEPA 2005 b . Human Health Risk Assessment Protocol for Hazardous Waste Combustion
Facilities. EPA530

- R

- 05

- 006. United Stated Environmental Protection Agency, Office of Solid Waste and Emergency Response , Washington, DC.

U.S. Environmental Protection Agency (USEPA). 2010. Reduced Risk Request for Dicamba
Herbicide Over

- The

- Top of Dicamba

- Tolerant Soybean. May 27, 2010.

U.S. Environmental Protection Agency (USEPA). 2010 Environmental Fate and Effects Division Response to a FIFRA Section 18 Emergency Exemption for Dicamba co

- formulated with 2,4

- D (LatigoTM) Use on Teff grown for grain, seed, and hay to control broadleaf weeds. Requested by the Oregon Department of Agriculture. May 24, 2010.

USEPA, 2011. Ecological Risk Assessment for Dicamba and its Degradate, 3,6

- dichlorosalicylic acid (DCSA), for the Proposed New Use on Dicamba

- Tolerant Soybean (MON 87708). Environmental Fate and Effects Division. Office of Pesticide Programs. Washington, D.C. March 8, 2011.

USEPA, 2012. Data Evaluation Record for MRID 47899517. Hea lth Effects Division. Office of Pesticide Programs, Washington D.C. December 7, 2012.

USEPA, 2014. Guidance for Assessing Pesticide Risks to Bees. Environmental Fate and E ffects Division. Office of Pesticide Programs. Washington, D.C. June 23, 2014.

USEPA, 2016 a . 3,6

- Diclorosalicyclic acid (DCSA): Benchmark Dose Analysis of a Reproduction Study. Health Effects Division. Office of Pesticide Programs, Washington D.C. March, 2 , 2016.
D431873

.

USEPA, 2016b. Dicamba DGA: Second Addendum to the En vironmental Fate and Ecological Risk Assessment for Dicamba DGA salt and its Degradate, 3,6

- dichlorosalicylic acid (DCSA) for
the Section 3 New Use on Dicamba

- Tolerant Soybean

. D426789. Environmental Fate and E ffects Division. Office of Pesticide Programs. Washington, D.C. March 24, 2016.39 Wall, D.A., 1994. Potato ( Solanum tuberosum ) Response to Simulated Drift of Dicamba, Clopyralid, and Tribenuron. Weed Science Vol. 42(1): 110

- 114.

Wax, L.M., L.A. Knuth, and F.W. Slife. 1969. Response of soybean to 2,4

- D, di camba, and picloram. Weed Science Vol. 17: 388

- 393.

Woodrow, J., Seiber, J., Baker, L. 1997. Correlation Techniques for Estimating Pesticide Volatilization Flux and Downwind Concentrations . Environ. Sci. Technol., 31:523

- 529

.

Woodrow, J., Seiber, J., Dar y, C. 2001. Predicting Pesticide Emissions and Downwind concentrations Using Correlations with Estimated Vapor Pressures . J. Agric. Food Chem.
49:3841

- 3846

.

Weidenhamer, J.D., G.B. Triplett, and F.E. Sobotka. 1989. Dicamba injury to soybean. Agronomy J ournal. Vol. 81: 637

- 643.40 

### Appendix 1: T

- REX Inputs and Outputs for Dicamba Use on Dicamba

- Tolerant Cotton41 TREX MODEL INPUTS You must enable macros for this spreadsheet to work correctly

These values will be used in the calculation of exposure estimates for foliar, granular, liquid and/or seed applications of pesticides.

Application No. Rate Day of Application

Chemical Name: Application Rate (lb ai/acre 1 1 0

Seed Treatment? (Check if yes) FALSE Seeding Rate (lbs/acre) 2 0.5 7

Use: 18.9 3 0.5 14

Product name and form: 4

% A.I. (leading zero must be entered for formulations <1% a.i.): 5

Application Rate (lb ai/acre) 1 6

Half-life (days): 8.4 7

Application Interval (days): 8

Number of Applications: 9

Are you assessing applications with
variable rates or intervals? yes 10

You MUST specify application day 11

12

What body weight range is assessed (grams)? Birds Mammals 13

Small 20 15 14

Medium 100 35 15

Large 1000 1000 16

17 18
19

20

21

22

23

24

25

26

27
28

29
30

Note: Sources of wildlife diet are assumed to be available for less than one year for this model.

Endpoints

Avian

Endpoint Toxicity value Indicate test species
below Optional Test Organism Body weight (g) Optional Test Species Name

LD50 (mg/kg-bw) 188.00 1

LC50 (mg/kg-diet) 10000.00 1

NOAEL (mg/kg-bw) 1

NOAEC (mg/kg-diet) 695.00 2

1.15 Mammalian

Acute Study Chronic Study
350 350

Endpoint Toxicity value Reference (MRID) LD50 (mg/kg-bw) 2740.00

LC50 (mg/kg-diet) Reported Chronic Endpoint 136.00 1

Is dietary concentration (mg/kg-diet) reported from
the available chronic mammal study? (yes or no) no

Enter dietary concentration (mg/kg-diet)

Estimated Chronic Diet Concentration Equivalent to Reported Chronic Daily Dose 2720 mg/kg-diet based on
standard FDA lab rat
conversion 100.00%

Enter the Mineau et al. Scaling Factor Assessed Species Inputs (optional, use defaults for RQs for national level assessments)

Size (g) of mammal used in toxicity study Default rat body weight is 350 grams You MUST specify application day in Columns F and G - you may enter up to 30 applications Chemical Identity and Application Information

Dicamba

5

Reset Model42 Summary of Risk Quotient Calculations Based on Upper Bound Kenaga EECs

Table X. Upper Bound Kenaga, Acute Avian Dose

- Based Ris k Quotients

Size Class (grams) Adjusted
LD50 EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropo

EEC RQ EEC RQ EEC RQ EEC RQ EEC

20 135.44 299.47 2.21 137.26 1.01 168.45 1.24 18.72 0.14 117.29 0

100 172.42 170.77 0.99 78.27 0.45 96.06 0.56 10.67 0.06 66.88 0

1000 243.55 76.46 0.31 35.04 0.14 43.01 0.18 4.78 0.02 29.94 0

Table X. Upper Bound Kenaga, Subacute Avian Dietary Based Risk Quotients

LC50 EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

10000 262.94 0.03 120.52 0.01 147.91 0.01 16.43 0.00 102.99 0.01

Size class not used for dietary risk quotients

Table X. Upper Bound Kenaga, Chronic Avian Dietary Based Risk Quotients

NOAEC (ppm) EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

695 262.94 0.38 120.52 0.17 147.91 0.21 16.43 0.02 102.99 0.15
Size class not used for dietary risk quotients

Table X. Upper Bound Kenaga, Acute Mammalian Dose

- Based Risk Quotients

EECs and RQs43 Size
Class (grams) Adjusted
LD50 Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropo

EEC RQ EEC RQ EEC RQ EEC RQ EEC

15 6022.06 250.70 0.04 114.90 0.02 141.02 0.02 15.67 0.00 98.1893 0.

35 4872.49 173.26 0.04 79.41 0.02 97.46 0.02 10.83 0.00 67.8619 0.

1000 2107.50 40.17 0.02 18.41 0.01 22.60 0.01 2.51 0.00 15.734 0.

Table X. Upper Bound Kenaga, Acute Mammalian Dietary Based Risk Quotients

LC50 (ppm) EECs and RQs

Sh ort Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

0 262.94 #DIV/0! 120.52 #DIV/0! 147.91 #DIV/0! 16.43 ##### 102.99 #DIV/0!

Size class not used for dietary risk quotients

Table X. Upper Bound Kenaga, Chronic Mammalian Dietary Based Risk Quotients

NOAEC (ppm) EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds/Large
Insects Arthropods

EEC RQ EEC RQ EEC RQ EEC RQ EEC RQ

27 20 262.94 0.10 120.52 0.04 147.91 0.05 16.43 0.01 102.99 0.04 Size class not used for dietary risk quotients

Table X. Upper Bound Kenaga, Chronic Mammalian Dose

- Based Risk Quotients

Size Class (grams) Adjusted
NOAEL EECs and RQs

Short Grass Tall Grass Broadleaf Plants Fruits/Pods/Seeds Arthropo

EEC RQ EEC RQ EEC RQ EEC RQ EEC

15 298.90 250.70 0.84 114.90 0.38 141.02 0.47 15.67 0.05 98.19 0

35 241.85 173.26 0.72 79.41 0.33 97.46 0.40 10.8 3 0.04 67.86 0

1000 104.61 40.17 0.38 18.41 0.18 22.60 0.22 2.51 0.02 15.73 044 

### Appendix 2. Dicamba and DCSA Residues from Dicamba

- Tolerant Cotton Crop Field
Trials

**Summary of Residues from Dicamba**

**- Tolerant Cotton Crop Field**  **Trials with DCSA as**  **a Dicamba Residue of Concern.**

Commodity Analyte Total
App.

Rate lb ae/A (kg ae/ha) PHI (days ) Residue Levels (ppm) 1

n Sample
Min. Sample

Max. LAFT 2 HAFT 2 Media

n Mean Std.

Dev.

**TRT 2 (Applications at Preemergence, 6**

**- leaf stage, an**  **d first white flower + 15 days; EP: Clarity)** 

Undelinted
Cotton seed Dicamba 2.0 (2.2) 49

- 105 13 < 0.02 < 0.02 < 0.02 < 0.02 0.02 0.02 N/A

5

- OH Dicamba 13 < 0.02 < 0.02 < 0.02 < 0.02 0.02 0.02 N/A

DCSA 13 < 0.02 0.23 < 0.02 0.23 0.02 0.04 0.06

**Combined**

**Res idues**  **13 <**  **0.06 <**  **0.28 <**  **0.06 <**  **0.28 0.06**  **0.09 0.06** 

Gin byproducts Dicamba 2.0 (2.2) 82

- 84 3 < 0.04 < 0.04 < 0.04 < 0.04 0.04 0.04 N/A

5

- OH Dicamba 3 < 0.04 < 0.04 < 0.04 < 0.04 0.04 0.04 N/A

DCSA 3 0.39 1.73 0.43 1.58 0.67 0.89 0.61

**Combined**
**Residues 3**  **< 0.47**  **< 1.82**  **< 0.53**  **< 1.66**  **0.75 0.97**  **0.61**

**TRT 3 (Applications at Preemergence, first open boll stage, and 7 days prior to harvest; EP: Clarity)** 

Undelinted
Cotton seed Dicamba 2.0 (2.2) 6

- 8 13 0.06 1.97 0.06 1.38 0.65 0.64 0.43

5

- OH Dicamba 13 < 0.02 0.0 2 < 0.02 < 0.02 0.02 0.02 N/A

DCSA 13 < 0.02 0.25 < 0.02 0.16 0.03 0.05 0.05

**Combined**
**Residues 13**  **< 0.12**  **< 2.24**  **< 0.10**  **< 1.56**  **0.71 0.71**  **0.48**

**TRT 4 (Applications at 6**

**- leaf, first white flower + 15 days, first open boll, and 7 days**  **prior to harvest; EP: Cla rity)** 

Undelinted
Cotton seed Dicamba 2.0

- 2.1 (2.2

- 2.4) 6

- 8 13 0.09 1.54 0.12 1.42 0.47 0.61 0.41

5

- OH Dicamba 13 < 0.02 < 0.02 < 0.02 < 0.02 < 0.02 < 0.02 N/A

DCSA 13 0.02 0.27 0.02 0.27 0.06 0.08 0.07

**Combined**
**Residues 13**  **< 0.13**  **< 1.83**  **< 0.16**  **< 1.72**  **0. 56**  **0.71 0.48** 

**TRT 4 (Applications at 6**

**- leaf, first white flower + 15 days, first open boll, and 7 days**  **prior to harvest; EP: Clarity)**

Gin byproducts Dicamba 2.0 (2.2) 6

- 7 3 3.09 23.6 3.13 23.0 14.9 13.7 10.0

5

- OH Dicamba 3 < 0.04 0.04 < 0.04 < 0.04 0.04 0.04 N/A

DCSA 3 1.70 6.29 1.78 6.17 4.50 4.15 2.22

**Combined**
**Residues 3**  **< 4.83**  **29.9 <**  **5.06 <**  **29.6 19.7**  **18.1 12.2** 

**TRT 5 (Applications at 6**

**- leaf, first white flower + 15 days, first open boll, and 7 days**  **prior to harvest; EP: MON 11968)**

Undelinted

Cott on seed Dicamba 2.0 (2.2) 7

- 8 4 0.17 0.72 0.20 0.62 0.41 0.41 0.23

5

- OH Dicamba 4 < 0.02 < 0.02 < 0.02 < 0.02 0.02 0.02 N/A45 **Summary of Residues from Dicamba**

**- Tolerant Cotton Crop Field**  **Trials with DCSA as**  **a Dicamba Residue of Concern.**

Commodity Analyte Total
App.

Rate lb ae/A (kg ae/ha) PHI (days ) Residue Levels (ppm) 1

n Sample
Min. Sample

Max. LAFT 2 HAFT 2 Media

n Mean Std.

Dev.

DCSA 4 0.02 0.17 0.02 0.12 0.04 0.06 0.04

**Combined**
**Residues 4**  **< 0.21**  **< 0.91**  **< 0.24**  **< 0.76**  **0.47 0.49**  **0.27**46 

### Appendix 3. T errPlant Inputs and Outputs for Dicamba Use on Dicamba

- Tolerant
Cotton

Green values signify user inputs (Tables 1, 2 and 4). Input and output guidance is in popups indicated by red arrows.

Table 1. Chemical Identity.

Chemical Name Dicamba

- DGA salt
PC code 128931
Use Cotton Application Method Ground

Application Form Spray Solubility in Water (ppm) 6100

Table 2. Input parameters used to derive EECs.
Input Parameter Symbol Value Units
Application Rate A 1 y

Incorporation I 1 none Runoff Fraction R 0.05 none

Drift Fraction D 0.01 none

Table 3. EECs for Dicamba

- DGA salt. Units in y.
Description Equation EEC
Runoff to dry areas (A/I)*R 0.05
Runoff to semi

- aquatic areas (A/I)*R*10 0.5 Spray drift A*D 0.01 Total for dry areas ((A/I)*R)+(A*D) 0.06

Total for semi

- aquatic areas ((A/I)*R*10)+(A*D) 0.51

Table 4. Plant survival and growth data used for RQ derivation. Units are in y.
Seedling Emergence Vegetative Vigor Plant type EC 25 NOAEC EC 25 NOAEC

Monocot 1.68 0.64 0.472 0.137

Dicot 0.123 0.0673 0.000513 0.000261

Table 5. RQ values for plants in dry and semi

- aquatic areas exposed to Dicamba

- DGA salt through runoff and/or spray drift.*
Plant Type Listed Status Dry Semi

- Aquatic Spray Drift

Monocot non

- listed <0.1 0.30 <0.1
Monocot listed <0.1 0.80 <0.1

Dicot non

- listed 0.49 4.15 19.49

Dicot listed 0.89 7.58 38.31
*If RQ > 1.0, the LOC is exceeded, resulting in potential for risk to that plant group.47 

## Appendix 4 : Runoff C alculations from SWCC and Resulting RQ values
in TerrPlant

Summary of Water Modeling of dicamba and the USEPA Standard Pond

Estimated Environmental Concentrations for dicamba are presented in Table 1 for the USEPA standard pond with the MScottonSTD field scenario. A graphical presentation of the year

- to

- year peaks is presented in Figure 1. These values were generated with the Surface Water Concentration Calculator (SWCC Version 1.106). Critical input values for the model are summarized in Tables 2

and 3.

This model estimates that about 22% of dicamba applied to the field eventually reaches the water body. The main mechanism of transport from the field to the water body is by runoff (76.7% of the total transport), followed by spray drift (23.1%) and erosio n (0.18%).

In the water body, pesticide dissipates with an effective water column half

- life of 106.0 days. (This value does not include dissipation by transport to the benthic region; it includes only processes that result in removal of pesticide from the complete system.) The main source of dissipation in the water column is metabolism (effective average half

- life = 107.2 days) followed by photolysis (9502 days) and volatilization (141341.2 days). In the benthic region, pesticide dissipates very slowly (6 22.2 days). The main source of dissipation in the benthic region is metabolism (effective average

half

- life = 622.2 days). The pesticide is about evenly distributed in the benthic region between the pore water and sorbed to sediment.

Table 1. Estimated En vironmental Concentrations (ppb) for dicamba.

Peak (1

- in

- 10 yr) 42.2

4

- day Avg (1

- in

- 10 yr) 41.7

21

- day Avg (1

- in

- 10 yr) 40.1

60

- day Avg (1

- in

- 10 yr) 35.6

365

- day Avg (1

- in

- 10 yr) 13.8

Entire Simulation Mean 8.4948 Table 2. Summary of Model Inputs for dicamba.

Scenario MScottonSTD

Cropped Area Fraction 1

Koc (ml/g) 13.4

Water Half

- Life (days) @ 25 °C 72.9

Benthic Half

- Life (days) @ 25 °C 423

Photolysis Half

- Life (days) @ 40

°Lat 105

Hydrolysis Half

- Life (days) 0

Soil Half

- Life (days) @ 25 °C 18

Foliar Half

- Life (days) 35

Molecular Wt 221

Vapor Pressure (torr) 3.41E

- 5

Solubility (mg/l) 6100

Table 3. Application Schedule for dicamba.

Date (Mon/Day) Type Amount (kg/ha) Eff. Drift

04/16 Ground 1.12 0.99 0.05

04/23 Ground 0.56 0.99 0.05

04/30 Ground 0.56 0.99 0.05

Figure 1. Yearly Peak Concentrations49 Table 4. Alternative dicamba runoff analysis based on MS cotton SWCC run at 2 lb/A (maximum annual application rate for dicamba based on a 1 lb a.e./A application and two 0.5 lb a.e./A appli cations.

Sources Contribution

factor Total mass (kg) based on 30 years Total mass applied over 30 year period Percentage

of dicamba over 30 year period Average

annual loss (%)

Runoff 0.7669 11.14

672 1.66 0.055

Erosion 0.0018 0.02634 0.0039 0.00013

to tal 0.7687 11.17 1.7 0.056

Comparison of the most sensitive terrestrial and aquatic endpoints for use in the runoff

calculations.

Comparing most sensitive IC 25 /NOAEC for non

- vascular aquatic plants and terrestrial plants. Most sensitive species are t he blue green algae (IC 50 /NOAEC of 0.061/0.005 mg ae/L) and soybean

IC 25 /NOAEC of 0.000513/0.000261 lbs ae/A.50 To compare, assume exposure is equivalent to a 1

- acre field covered with 1 inch of water. Therefore the EEC in lb/A that compares to an IC 50 of 0.061 mg ae/L for blue

- green algae can be considered following Equation 1 below:

Equation 1.

EEC lb a.e./Acre = (Z mg/L) * (102,790 L water/ Acre

- in) * (1 inch) * (1 lb/ 453,592 mg) which

reduces to:

Equation 2.

EEC lb a.e./Acre = (Z mg/L) * (0.226613 )

EEC lb ai/A = 0.061 mg/L * 0.226613 = 0.0138

and the EEC in lb/a that compares to a NOAEC of 0.005 mg ae/L for blue

- green algae would be

EEC lb ae/A = 0.005 mg/L * 0.226613 = 0.0011. These endpoints are approximately 1

- 2 orders of magnitude less sens itive than the soybean endpoints. Therefore, the soybean endpoints should be

used in the revised TerrPlant runoff claculations.

Table 5. RQ values calculated in TerrPlant for plants in dry

and semi

- aquatic areas exposed to Dicamba DGA salt through

runof f. Conservative assumptions of 2 lb a.e/A application rate and 0.06% loss through runoff and erosion.

Plant Type Listed Status Dry Semi

- Aquatic

Monocot non

- listed <0.1 <0.1

Monocot listed <0.1 <0.1

Dicot non

- listed 0.17 0.26

Dicot listed 0.32 0.48