UNI TE D ST A TES ENVIRON M E NTAL PROTECT I ON AGENCY
WASHINGTON D.C., 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

P

C Co de: 098701
DP Barcode: 0424922

MEMORANDUM Date March 10, 2015

Subject:

To:

From:

Reviewed:

Through: Regis t ration Review

- Preliminary Problem Form ulation for Ecological Risk and
Environmental Fate, Endangered Species

, and Drinking Water Assessments for Phenmedipham

Miguel Zavala

, Chemical Revi ew Manager
Neil Anderson

, Acting Branch Ch ie f
Risk Management and Impl ementation Bran c h 3
Pesticide Re-evaluation Division (PRD)

Amy Blankinship

, Chemist

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

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En vironmental Risk Bran ch 6 ./

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Environmental Fate and Effects Di vis ion

Office of Pesticide Pro grams

Monica Wait

, Risk Assessm e nt Process Leader

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Environmental Risk Branch 6
Environmental Fate and Effects Division

Office of Pesticide Programs

Mark Co rbin

, Branch Chief 

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Environmental Fate and Effects Division
Office of Pesticide Program s

The E nvir onme ntal Fate and Effects Divi sion (EFED) has completed the preliminary prob l em formulation (attached) for the ecologica l ri sk, environmental fate, e ndangered spec ies

, and drinking water assessments to be conducted as part of the registration review of the herbicid e, phenmedipham. The problem formulation draws on inform ation from studies submitted by the

technical registrants in response to data requirements. This document provides an overv ie w of

Page I of 48what is currently known regarding the environmental fate and ecological effects associated with phenmedipham and its degradates and outlines uncertainties regarding attributes of the parent compound and its transformation products. It describes the preliminary ecological risk hypothesis and the processes that will be used during the completion of drinking water and ecological risk assessments in support of Registration Review . This document also recommends
studies to include in a data call

- in (D CI) to address uncertainties surrounding the environmental fate and potentia l ecological effects of phenmedipham

.

Page 2 of 48

## Problem Formulation
for the Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Assessments
in Support of the Registration Review of Phenmedipham

PC Code: 098701

CAS #: 13684

- 63

- 4

Environmental Fate and Effects Division:
Environmental Risk Branch V I
William P. Eckel, Ph.D., Senior Science Advisor Amy Blankinship, Chemist

Reviewed by:
Monica Wait

, Risk Assessment Process Leader
Mark Corbin , Branch Chief U. S. Environmental Protection Agency Office of Pesticide Programs 1200 Pennsylvania Ave., NW
Mail Code 7507P Washington, DC 20460

Page 3 of 48Table of Contents

1. Executive Summary

................................ ................................ ................................ ................. 5
2. Introduction

................................ ................................ ................................ ............................. 5
3. Use Characterization

................................ ................................ ................................ ................ 7
4. Conclusions from Previous Risk Assessments

................................ ................................ ........ 8
4.1 Clean Water Act Programs

................................ ................................ ............................... 8
5. Environmental Fate and Transport

................................ ................................ .......................... 9

6. Receptors

................................ ................................ ................................ ............................... 12

7. Exposure Pathways of Concern

................................ ................................ ............................. 21
8. Analysis Plan

................................ ................................ ................................ ......................... 22
8.1 Stressors of Concern

................................ ................................ ................................ ....... 22
8.2 Measures of Exposure

................................ ................................ ................................ .... 22
8.3 Measures of Effect

................................ ................................ ................................ ......... 23
9. Endangered Species Assessment

................................ ................................ ........................... 23 10. Endocrine Disruptor Screening Program

................................ ................................ ............... 24 11. Preliminary Identification of Data Gaps

................................ ................................ ................ 25
11.1 Environmental Fate

................................ ................................ ................................ ..... 25
11.2 Effects

................................ ................................ ................................ ......................... 26
12. References

................................ ................................ ................................ .............................. 33 Appendix A. Toxicity Data for Phenmedipham and Desmedipham

................................ ....... 34 Appendix B. Predictive Data for Parent Phenmedipham and its Degradates from QSAR Modeling using Ecosar v1.11

................................ ................................ ................................ ... 36 Appendix C. Screening Level Models to Evaluate Potential Importance of Drinking Water and Inhalation Exposure Pathways

................................ ................................ ........................... 41 Appendix D. Data Justification Tables for Non

- guideline Studies

................................ .......... 43

Page 4 of 48

## 1. Executive S ummary

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem formulation for the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the registration review of phenmedipham (PC code
098701 ) . The problem formulation describes the methods to be used for the drinking water and ecological risk assessments in support of registration review and provides an overview of the environmental fate, ecological effects, and potential risks as sociated with the use of phenmedipham as well as uncertainties uniqu e to its risk assessment

. This document also identifies additional studies that would be beneficial to the conduct of an ecological risk

assessm ent.

Data needs for ecological effects are:

• Adult Honey Bee Chronic Oral Toxicity (non

- guideline) using TGAI

• Larval Honey Bee Acute Oral Toxicity (non

- guideline) using TGAI

• Larval Honey Bee Chronic Oral Toxicity (non

- guideline) using TGAI

• Field Trial of residues in pollen and nectar (non

- guideline)

- may be waived pending the results of the lower tier larval and adult honey bee acute and chronic oral toxicity studies

• Semi

- Field Testing for Pollinators (non

- guideline )

— may be waived pending the results of the lower tier larval and adult honey bee acute and chronic oral toxicity studies

• Field Testing for Pollinators (850.3040)

— may be waived pending the results of the lower tier larval and adult honey bee acute and chronic oral toxicity studies

• Freshwater Subchronic Sediment Toxicity (850.1735) using TGAI for two species of freshwater invertebrates

• Estuarine/marine Subchronic Sediment Toxicity (850.1740) using TGAI for one species of estuarine/marine invertebrates

It is noted that currently there are no s ubmitted chronic aquatic fish or invertebrate toxicity studies for phenmedipham and the acute toxicity studies for fish and aquatic invertebrates are for qualitative use only. However, based on the lines of evidence ( i.e., toxicity studies from the open l iterature, estimated exposure concentrations, and quantitative structure activity relationship models), these studies are not requested at this time. If there is a change in the use profile for phenmedipham ( i.e., additional use sites and/or increase in t he use rates for existing registered uses), then these data gaps may need to be re

- evaluated, and additional data may be necessary.
Data needs for environmental fate and exposure assessment are:

• Environmental Chemistry Methods and independent laboratory va lidations for p arent phenmedipham and its major d egradate s in Soil and W ater (850.6100)



## 2

. Introduction

Phenmedipham ( PC 098701; Figure 1 ), a selective systemic herbicide belonging to the phenyl carbamate family, is used to control broad

- leaved weeds (post emergence) on red beets and spinach (for processing and seed)

. It affects photosynthesis in target plants by interfering with the "Hill Reaction" during photosynthesis II. Currently, there are two technical use products and

Page 5 of 48one end

- use product label ( emulsifiable concentrate (EC) ) for phe n medipham . The chemical may be applied as either a broadcast ground application, band treatment, or aerially. Details of treated crops and areas as well as application rates and methods are provided in Section 3 of t his
document.

Figure 1 : Chemical structure of phenmedipham (PC Code 098701 ) and its major degradate
MHPC

Chemical Structure of major degradate, MHPC

Page 6 of 48Laboratory environmental fate studies have shown that there is one major degradate of phenmedipham, methyl

- 3

- hydroxyphenyl

- carbamate (MHPC). MHPC appears to show similar persistence as the parent, but it is more mobile.

T oxicity data for desmedipham (PC c ode 104801) , another herbicide with similar chemical structure, environmental fate properties, and toxicology as phenmedipham , was used to support
th e risk assessment for the Reregistration Eligibility Decision (RED) when phenmedipham

specific data were no t available (USEPA 2005)

. The chemical structures of desmedipham and phenmedipham differ by the placement of one methyl group.

EFED evaluated the most recent ecologic al risk assessments for phenmedipham in association with the updated toxicity, exposure , and usage information to determine if sufficient data are
available or if further updates are needed to support registration review. In addition, EFED considered the latest Agency science policies and risk assessment methodologies.



## 3. Use Characterization

The chemical profile produced by Biological and Economic Analysis Division (BEAD), located
in the registration review docket (USEPA 2014) , lists the use patterns of maximum exposures for
the current uses of phenmedipham

. Phenmed i pham is currently registered for use on spinach (processing and seed) and red (table) beets. The former major use on sugar beets is no longer found on any end

- use product labels, therefore, it will not be considered in this assessment. However, if registrants pet ition to add sugar beets back onto end

- use products, then additional data may be necessary.

BEAD’s chemical profile includes both a summary of labeled uses as well as a summary of available reported usage data. The Screening Level Usage Analysis (SLUA) an d chemical profile reports conduc ted by BEAD showed usage of phenmedipham on spinach in the top three production states (California, New Jersey and Oklahoma) , based on available data from 200 8

— 2012 (USEPA, 2014). The total us age of phenmedipham for spinac h was 3,100 lbs with a total of 4,389 acres treated, primarily by ground application (aerial application only reported for California). Based on the usage data from California Department of Pesticide Regulation (CalDPR; year 2010

- 2012), phenmedipham was u sed on average on 176 acres of beets (table) and 1,400 acres of spinach in California

.

The use profile to be utilized for EFED’s risk assessment includes the terrestrial uses described
in Table 1

. There is one end

- use product label for phenmedipham for use on spinach and red beets (EPA Registration 264

- 616). The highest single maximum use rate is 0.9 75 lbs a .i. /A ( both

crops )

. Based on the label, this single maximum use rate should only be used on well established crops that are not under stress. For less established plants (e.g., 2

- leaf stage instead of 4

- 6 true leaf stage for spinach), a split application of 0.488 lb a.i./A may be applied with a reapplication at the same rate four to six days later. The maximum yearly application rate is also 0 .975 lb a.i./A. The label indicates to not add additional wetting agents or other spray adjuvants. EFED will use application scenarios that result in maximum exposure scenarios for a given use for the
risk assessment.

Page 7 of 48Table 1

. Profile of currently registered u ses of Phenmedipham

Crop Max imum Single App lication
Rate (lb a.i. /acre ) Annual
Maximum Application
Rate Geographic

R estrictions Application
Method (s) End

- use Product
Labels

Spinach (for processing and seed) 0.975 1 0.975 None Ground (broadcast, banded) or
aerial 264

- 616 Red (table) beets

1 For less established plants (e.g., 2

- leaf stage instead of 4

- 6 true leaf stage for spinach), a split application of 0.48 75 lb
a.i ./A may be applied with a reapplication at the same rate four to six days later.



## 4. Conclusions from Previous Risk Assessments

The Agency has conducted previous ecological risk assessments and drinking water assessments
for phenmedipham that serve as a basis for this problem formulation. Results of the most recent

assessment are briefly summarized below

.

Reregistration Eligibility Decision (RED)

A RED was completed for phenmedipham in 2005 (USEPA 2005) . Overall, the agency’s

assessm ent indicated that use of phenmedipham on sugar beets, red (table) beets, spinach, and
Swiss chard should not result in acute or chronic risks to birds or mammals ; all RQs below the
LOC

. B ased on the available acute contact data (supported by the desmedip ham honey bee study), the assessment anticipated that non

- target insects will not be at significant acute risk from phenmedipha m exposure

. The assessment assumed that the toxicity of the major degradate,

MH PC , was similar or lower than the parent compound

. Submitted data for acute rainbow trout
and acute Daphnia magna studies indicated that MHPC is less toxic to aquatic invertebrates than the parent compound , and therefore, it was indicated that acute or chronic risk from the degradate is not anticipated. Acceptable acute toxicity data for freshwater fish, invertebrates or aquatic nonvascular plants for phenmedipham were not available, and therefore, toxicity data from desmedipham was used. A data waiver for chronic toxicity data for aquatic animals was

re quested by the registrants and was granted given the instability of parent phenmedipham. The
RED stated that phenmedipham use should not result in acute or chronic risk to freshwater fish
and invertebrates. Additionally, the RED indicated, that, ph enmedip ham does not appear to present a risk to off

- site non

- target terrestrial or aquatic vascular and nonvascular plants

.



## 4.1 Clean Water Act Programs

Phenmedipham is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No Total Maximum Daily Load (TMDL) c riteria

Page 8 of 48have been developed for phenmedipham

. Based on its chemical structure, this compound falls under the 50 microgram per liter New York State drinking water standard for “unspecified organic contaminants” (10 NYCRR Part 5, Public Water Systems). Aquatic benchmarks have not been established for phenmedipham ( http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm )

.



## 5

. Environmental Fate and Transport

The environmental fate database is complete and consists of acceptable and supplemental
studies. These studies show that phenmedipham exhibits low to moderate persistence under most
environmental s cenarios. Hydrolysis and aerobic soil biodegradation occur relatively rapidly at neutral and alkaline pH, but under acidic conditions phenmedipham is more stable. (Calculated hydrolysis half

- lives were 50 days, 14.5 hr, and 9.6 rnin, respectively at pH 5,7, and 9.)

In aerobic soil metabolism studies, the half

- life is 20 days in pH 6.8 soil; however, under acidic conditions these degradation rates are considerably slower, indicating that phenmedipham may persist in acidic soils for several weeks or longer . A erobic soil metabolism half

- life is 120 days in pH 5.0 soil

, but degrades with a half

- life of 79 hours in sandy loam soil at pH 7.
Several su pplemental studies show that phenmedipham is adsorbed strongly by soil surfaces, and its potential to leach into groundwater is low in several aged and unaged soil column studies. Because the potential for phenmedipham to volatilize from soil or water surf aces is very low (VP= 1E

- 11 mmHg), inhalation exposure to mammals or avian species is expected to be low.

The major transformation product, MHPC appears to show similar persistence as the parent, but
it is more mobile. MHPC residues were never >15% of the total residues, except in the hydrolysis study and aerobic aquatic metabolism studies. In the hydrolysis study, MHPC reached a maximum of 54.7% at 3 days in a pH 7 aqueous solution. A minor degradate, m eta

- toluidine, was observed in hydrolysis and anaerobi c metabolism studies. In an aerobic aquatic metabolism study, which provided limited supplemental data because the sediments were anaero b ic, phenmedipham degraded with half

- lives of 4.7

- 16.6 days in two water

- sediment systems. MHPC was the major transforma tion product, reaching at a maximum of about 77% after one day

.

Registrant

- submitted data characterizing the physical, chemical, fate and transport characteristics
associated with phenmedipham are summarized below in Table 2

.

Table 2 : Physioc hemical Properties and Environmental Fate Characteristics of Phenmedipham

Parameter Value 1 Description Source (MRID) Selected Physical/Chemical Parameters

CAS No.: 13684

- 63

- 4

IUPAC name 3

- methoxycarbonylaminophenyl 3’

- methylcarbanilate

CAS name 3

- [( methoxycarbonyl)amino]phenyl(3

- methylphenyl)carbamate

Smiles c1ccc(C)cc1NC(=O)Oc2cccc(NC(=O)OC)c2 (Parent)

O=C(OC)Nc1cccc(O)c1 (MHPC)

Page 9 of 48Molecular Mass
of Phenmedipham (Molecular Formula) Parent: 300.31

amu (C16H16N2O4)

MHPC: 167.16 amu (C 8 H 9 NO 3 ) Herbicide Handbook, Weed Science Society of America

7 th ed. 1994 [WSSA]

Footprint database http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/516.htm Vapor pressure (25°C) 10E

- 11 mmHg
at 25°C WSSA

Aqueous solubility (25 ° C) ppm 4.7 mg/L 00142752

Apparent (the
sum of the
ionized and non

ionized forms ) Log octanol

- to

water partition coefficient (K OW ) Kow = 3890 at pH4 (log Kow = 3.6)

Log P = 3.86 Log D = Log P

up to pH 12

LogKow = 3.72 WSSA

www.chemicalize.org

40435102

Persistence

Hydrolysis: Half

life (25±1 ° C) 50 days pH 5 14.5 hrs pH 7 9.6 min pH 9 40502708 (Acceptable)

Aqueous Photolysis: Half

life (25±1 ° C) stable 42429901 (Acceptable)

Soil Photolysis:
Half life (25±1 ° C; pH: 5.4) 79 hours 00142742 (Acceptable)

Aerobic Soil
Metabolism: Extrapolated
Half

- life (25±1°C) 20 days, 120 days; German

soils (2.3 Hatzenbuhl, 2.2 Neuhofen) 00142744, Supplemental

MHPC half

- life 2.3 Hatzenbuhl 72.2 days; 2.2 Neuhofen 41.5 days

Anaerobic Soil
Metabolism , half

life 12.5 days in flooded Loamy

sand system 42099101, 42990301 (Acceptable)

Aerobic Aquatic
Metabolism: Extrapolated
Half

- life (25±1°C) 4.7 days (German loam

sediment

stream water)

16.6 days (German sand

sediment

stream w ater) Total
system log

- linear
half

- life 46302501 (Supplemental)

Mobility

Soil

- water partition Kd 28 pH5.6
1.93%OC Parent: 46286302 (Invalid), 00142747 (Supplemental)

Page 10 of 48coefficients (K d

ads )

Organic carbon

normalized partition coefficients (K OC )

(Parent) 1/n =0.99 (Neuhofen)

Kd 314 pH5.0 99%OC,
1/n=1.5 (Hatzenbuhl) 46286301 (Supplemental, non

- guideline)

Column leaching: 40765701, 40765702, 43209301, 00142749, 42099102

Soil

- water partition coefficients (K d

ads )

Organic carbon

normalized partition coefficients (K OC )

(MHPC) Speyer 2.1 sand

212 (pH6, 0.475%OC)

Speyer 2.2 loamy sand 138 (pH5.7, 1.93%OC)

Speyer 2.3 sandy loam 58 *Ph5, 0.99%OC)

Loamy sand 333 (pH5.9,

1.03%)C)

Sandy clay
loam 470 (pH6.3, 0.33%OC) MHPC: 46286303 (Supplemental)

Field Dissipation

Terrestrial Field Dissipation : Half

life and DT 75 Leaching depth 13.3 days Fresno CA sandy loam

pH 7.3,
0.12%OC 42891601, 46412301 (Supplemental)

111

- 136 days Crown
Point IN loamy sand

pH6.4,
2.2%OC 42891601, 46412301(Supplemental)

5.8 to 39.9 days Germany (4 locations) 46412302 (Supplemental)

Fish Bioconcentration

Page 11 of 48Fish
Bioaccumulation

Factors (28 d BCFs for bluegill sunfish) 165X whole
fish
1518X viscera

19X edible

tissue
43X inedible
tissue 40912801 (Acceptable)

Abbreviations: ° C

- degrees Celsius; d = day; DT

- disappearance time; hrs. = hours; in. = inch; l = liters; kg = kilograms; LOQ = level of quantitation; < = less than;

Notes:

1 Except for one replicate that showed the paren t leached below 6in. depth.

The primary metabolite of phenmedipham was shown to be methyl

- 3

- hydroxyphenylcarbamate (MHPC). It was detected at a maximum of 14.0% among all studies, except the hydrolysis and aerobic aquatic metabolism studies. A minor degradate observed in the aerobic aquatic metabolism study was m eta

- toluidine. The transformation pathway proposed by the author is
consistent with the structure and the two transformation products observed in various studies: phenmedipham is cleaved at th e amino

- carbonyl linkage yielding methyl 3

- h ydroxyphenylcarbamate (MHPC) and m

- toluidine, with ultimate formation of carbon
dioxide. Below

, T able 3 presents identified major degradates and their maximum percent of applied radioactivity.

Table 3

. Major De gradates identified and maximum percent of applied radioactivity in
the fate stud ies

.

Degradates Structure Study Type (Reference) Percent of applied radioactivity (%) at

pH5 pH7 pH9

MHPC methyl

- 3

- hydroxylphenylcarbamate See Figure 1 Hydrolysis

Aerobic Aquatic
metabolism 54.7% at 3 days (pH 7)

77% at 1 day



## 6

. Receptors

Tables 4 and 5 provide a summary of the taxonomic groups tested to characterize the potential acute and chronic ecological effects of phenmedipham

. In addition, the table s provide a preliminary overview of the potential acute toxicity of phenmedipham by providing the a cute toxicity classifications. Desmedipham toxicity data were used to bridge data gaps for phenmedipham. The available toxicity data for phenmedipham and desmedipham are presented
in Appendix A

.

Aquatic Organisms

Page 12 of 48Acceptable acute toxicity data for freshwater fish and invertebrates were not available for phenmedipham (submitte d studies classified as invalid: did not measure test concentrations, low dissolved oxygen, effects in solvent control group) . In the RED, acute toxicity aquatic animal
data and non

- vascular aquatic plant data from desm edipham were used to bridge phenmedipham
d ata gap s, and this approach will be used for reg istration review . However, in the p roblem
f

ormulation for registration review of desmedipham, the freshwater fish and invertebrates studies were downgraded to supplemental since desmedipham concentrations

, which is known to be unstable in water, were not measured in the study (studies conducted in a static test system) ; new studies were requested in the desmedipham problem formulation (USEPA 2011)

. Results of acute toxicity studies show desmedipham is at least moderately toxic to freshwa ter fish (rainbow
trout LC 50 = 1.7 mg a.i. /L , MRID 00116714; bluegill sunfish LC 50 = 6 mg a.i. /L , MRID 00116713) and freshwater invertebrates ( Daphnia magna EC 50 = 1.88 mg a.i. /L

, MRID 00116712). However, since test concentrations were not measured in the study, these valu es may underestimate the LC/EC 50 value. A n acute toxicity study with an estuarine/marine mysid shrimp ( Americamysis bahia ) for parent desmedipham resulted in an LC 50 value of 1.2 mg a.i./L (MRID 48587107)

.

Acute toxicity data for the major phenmedipham de gradate, MHPC, were available for
freshwater fish and invertebrates (MRID 45414203 and 45414202, respectively) . The acute LC 50 value for rainbow trout and EC 50 value for Daphnia magna were classified as slightly toxic with toxicity values of 74.1 and 14 mg a.i./L, respectively. In the phenmedipham RED, the degradate study with the rainbow trout was reported as invalid (due to use of dechlorinated water

, aeration

, and higher than recom mended water hardness and pH). This study was re

- evaluated for registration review and has been upgraded to supplemental. These data indicate that the degradate is less toxic than parent phe n medipham/desmedipham.

Submitted chronic data for freshwater f ish and invertebrates and acute data for estuarine/marine fish are not available for either phenmedipham

, desmedipham or their degradates

. A study by
Vidal et al ., 2012, evaluated effects on freshwater invertebrate, Daphnia magna and Daphnia longispina , r eproduction (number of neonates produced) from a 21

- day exposure to phenmedipham

, desmedipham and a formulation containing both active ingredients (Betanal® Expert) ; in the studies, the test solutions were renewed every other day . The reported 21

- day
EC 50 , EC 20 and EC 10 values (NOAEC/LOAEC values were not reported) for phenmedipham, based on average number of neonates, were 0.218, 0.096 and 0.059 mg/L for D

. magna and were 0.253, 0.156, and 0.118 mg/L for D

. longispina

. It is noted that the 95% confidence intervals overlapped between the EC 50 and EC 20 and between the EC 20 and EC 10 , thereby introducing uncertainty in the reliability of the ECx value. In this study, t he phenmedipham 48

- hr EC 50 values (immobility) were 1.75 and 2.1 mg a.i./L for D. magna and D. longispina , respectively

, which is in good agreement with the EC 50 value for Daphnia magna above (1.88 mg a.i./L; MRID 00116712)

.

EFED attempted to see if quantitative structural activity relationships (QSAR) could be used to estimate the toxicity of p henmedipham and MH PC for estimates of acute and chronic toxicity for
fish and freshwater invertebrates (Appendix B ). Predicted fish acute LC 50 value s ranged from
2.65

- 4.92 mg /L for parent phenmedipham. While it is noted that the empirical acute fish LC 50

Page 13 of 48values may be underestimating toxicity, the predicted values are in good agreement with th ose acute fish LC 50 values (1 .7 and 6 mg/L ; Table 4) from submitted studies . The predicted chronic fish toxicity values ranged from 0.155

- 0.516 mg/L. For daphnids, the predicted acute toxicity values were more variable and ranged from 0.00184

- 4.27 mg/L

, and therefore were overall in less agreement with the empirical EC 50 value of 1.88 mg/L (Table 4). Estimated chronic toxicity
values for daphnids w ere also variable a nd ranged from 0.004

- 0.662 mg/L. For the major degradate, MHPC, the predicted acute toxicity values for both fish (143

- 192 mg/L) and daphnids (35.7

- 122 mg/L) were greater than the values from the submitted studies (74 and 14 mg/L for
fish and daphnids , re spectively ) . The predicted chronic toxicity values for MHPC for fish and daphnids ranged from 14.8

- 16.6 mg/L and 6.8

- 13.8 mg/L, respectively.

P arent phenmedipham is short

- lived in water at neutral and basic pH s , but longer at acidic pH (1 4.5 h r at pH 7 a nd 10 minutes at pH 9 , yet 50 d ays at pH 5 , MRID 40502708 ). However,

MH P C is anticipated to be stable under soil and aquatic conditions. Based on estimated environmental concentrations (EEC s ) calculated in the 2005 RED, the peak EEC for parent phenmedipham and MH PC from a single application at 0.975 lb a.i./A was 16.95 and 4.18 μg/L;
21 and 60

- day EECs were very similar to peak EECs (USEPA 2005). Even though the empirical parent phenmedipham LC/EC 50 acute toxicity values may underestimate toxic ity due to anticipated hydrolysis, based on the peak EEC for phe n medipham, the actual toxicity values
would need to be at least 50 times lower to exceed the non

- listed level of concern for fish and aquatic invertebrates (LOC of 0.5; (1700 μg/L (rainbow tro ut) ÷ 17 μg/L (peak EEC) ÷2 = 50). Additionally, the acute toxicity LC 50 value for the estuarine/marine mysid shrimp was in good agreement with the reported EC 50 value for the freshwater invertebrate. The study with the mysid shrimp was conducted using a flow

- through test design and test concentrations were measured, thereby, resulting in greater confidence in the reported LC 50 value. Furthermore, the predicted acute values for freshwater fish were also in good agreement with the empirical values.

In regards to chronic toxicity values, f or fish , the predi c ted chronic toxicity values for fish were ≥9 times the phenmedipham peak EEC. While there is less reliability with the predicted chronic fish toxicity values for MH PC since the predicted acute values were greater than the empirical
values , the predicted chronic values and the empirical acute LC 50 value for MH PC are >3,500 and >17,000 times greater than the peak MH PC EEC. For chronic exposure for Daphnia , using the lowest reported ECx value from the ope n literature study (0.059 mg/L) for phenmedipham, this value is 3.5 times greater than the peak EEC. In this stud y , test solutions were renewed every other day (representing a potential pulsed exposure due to anticipated hydrolysis), and the EEC
represents a single application at the single and yearly maximum rate. It is noted that the predicted acute and chronic values for Daphnia for phenmedipham and MH PC were quite
variable and not always in good agreement with empirical values

. However, for daphnids, the predicted chronic values and the empirical acute E C 50 value for MH PC are > 1,600 and > 3,000 times greater than the peak MH PC EEC

. Estuarine/marine fish acute or chronic or estuarine/marine invertebrate toxicity data are not available. However, based o n the available data, it is not anticipated that estuarine/marine fish or invertebrates would be substantially different in their sensitivity to phenmedipham or MH PC . O verall, based on this evaluation,
additional acute and chronic toxicity data for fish o r aquatic invertebrates are not requested for parent phenmedipham or MH PC

.

Page 14 of 48Sediment toxicity data are not available for phenmedipham. A 28

- day sediment study with overlying water containing desmedipham using the midge, Chironomus riparius , reported a 28

- day NOAEC of 0.27 mg (desmedipham plus EHPC)/L, based on development rate (MRID 48587108). This study is classified as supplemental, qualitative (did not have reliable measurements of test concentrations in pore water or sediment). The NOAEC of 0.27 mg/L (270 μg/L) is 16 times greater than the peak EEC (17 μg/L; representing overlying water), however, this study was not conducted using phenmedipham treated sediment which is the preferred exposure route for sediment testing (estimated sediment concentration Koc (est.) x Peak EEC ; 1860 L/kg

- oc x 0.017 = 32)

. F or parent phenmedipham , the log Kow is 3. 72 (MRID 40435102 ) and its mobility in soil is anticipated to be low (Koc ≥1,450) . Since the half

- life at pH 7 and above is less than 10d, chro ni c sediment st udies with parent are not requested

. However, as effects were observed in the study utilizing exposure via overlying water with desmedipham, 10

- day subchronic toxicity tests with phenmedipham (via exposure to phenmedipham

- treated sediment) with freshwater and estuarine/marine invertebrates are recommended. The hydrolytic degradate, M HPC, is not expected to partition to sediment, with Koc and log Kow values of 58 L/kg

- oc (MRID 46286303; lowest non

- sand value) and 1.41 ( EpiSUITE

- estimated ) , respec tively. Due to this hydrophilicity, no sediment tests are being requested for M HPC.

A green algae study was available for phenmedipham, whereas several aquatic non

- vascular plant toxicity data (green algae, freshwater and marine diatom, cyanobacteria) t oxicity data and a vascular aquatic plant (duckweed) toxicity study were available for desmedipham. The most sensitive aquatic non

- vascular plant toxicity value was for the freshwater diatom, Navicula pelliculosa , with an I C 50 value of 0.14 mg a.i./L and a NOAEC of <0.12 mg a.i./L (40%
inhibition at lowest concentration at 96

- hrs ; MRID43053503 ) . The I C 50 value for the vascular plant, Lemna gibba , was >1.02 mg a.i./L. Vidal et al ., 2012, also examined the effects on both green algae ( Pseduokirchneriella subcapitata, Chlorella vulgaris, and Chlamydomonas pseduocostata ) and Lemna minor . The reported phenmedipham EC 50 and EC 10 values (based on growth rate ) for the green algae were ≥0.066 and ≥0.002 mg a.i./L , respectively, and the EC 50 was 0.066 mg a.i ./L for Lemna minor

. In this study, for desmedipham, the green algae EC 50 values were ≥0.06 5 mg a.i./L and was 0. 225 mg a.i./L for Lemna minor

.

The single registered end

- use label for phenmedipham indicates that the formulation contains the
toxic inert i ngredient, isophorone ( EPA Reg# 264

- 616) . Submitted aquatic animal or plant toxicity data for isophorone are not available. However, other information indicates an acute
LC 50 value of 224 mg/L for fish (bluegill sunfish) and acute EC 50 /LC 50 values of 12.9

– 117 mg/L for freshwater ( Daphnia magna ) and estuarine/marine (mysid shrimp) invertebrates (USEPA 1980). An aquatic plant toxicity (green algae and saltwater diatom) value of ≥105 mg/L was also reported. Additionally, the reported chroni c value from an early life

- stage toxicity study with sheepshead minnow fish was 110 mg/L. This toxicity data suggests that this inert ingredient is less toxic than parent phenmedipham.

Page 15 of 48Table 4 . Summary of the Most Sensitive Endpoints from Aquatic Toxi city Studies for Phenmedipham

Taxonomic Group Study Type Tested Species Toxicity Value (95% conf.
intervals ) (mg a.i./L) Acute Toxicity
Classification Source (Study Classification)
Comments

Freshwater
fish 1 Acute Rainbow trout ( Oncorhynchus mykiss ) 96

- Hr LC 50 = 1 .7 2 Moderately
toxic 00237908 ( Supplemental 3 )

Chronic No data

Freshwater
invertebrates Acute Water Flea ( Daphnia

magna ) 48

- Hr E C 50 = 1.88 2 Moderately
toxic 0235009 (Supplemental 3 )

Chronic Water Flea ( Daphnia

magna ) 21

- d EC 10 = 0.059 4 NA Vidal et al. 2012 (Qualitative) Based on average number of neonates produced

Estuarine/
marine fish Acute No data

Chronic No data

Estuarine/
marine
invertebrates Acute Mysid shrimp ( Americamysis
bahia ) 96

- hr LC50 = 1.2 (1.0

- 2.0) 2

Slope: NA Moderately
toxic 48587107 (Acceptable)

Chronic No data

Aquatic plants and algae Vascular Duckweed ( Lemna gibba ) IC 50 >1.02
NOAEC = 1.02 2 N/A 43053505 ( A cceptable) Tier I study

Non

vascular Freshwater
Diatom
Navicula pelliculosa IC 50 = 0.14 (0.12

- 0.17)
NOAEC
<0.120 2 ,5 Slope: 1.8 N/A 43053503 (Acceptable)

1 Freshwater fish may be surrogates for aquatic

- phase amphibians.

2 Based on desmedipham data

3 Study downgraded in desmedipham problem formulation and a new study was requested. Test solutions not measured in the static system and therefore, reported toxicity value may underestimate toxicity

. 4 NOAEC/LOAEC values not reported in this study. EC 50 , EC 20 and EC 10 values reported in study. It is noted that the 95% confidence intervals overlapped between the EC 50 and EC 20 and between the EC 20 and EC 10 , thereby introducing uncertainty in the actual ECx value.

5 Based on the data, an IC 05 value was not considered rel iable.

Terrestrial Organisms

Phenmedipham is practically non

- toxic to birds on an acute oral basis and a dietary basis, and it is practically non

- toxic to mammals on an acute oral exposure basis ( Table 6 ). In the acute oral mallard duck study (MRID 40623501) with phenmedipham, a split

- dosing method was used
whereas the 2

, 100 mg a.i./kg

- bw dose was split into two equal portions with one dose given in the morning and the second dose later in the afternoon. There was no mortality, clinical signs of toxicity or effects on body weight or food consumption observed in the study; this study is classified as Supplemental. There were no effects observed in the acute oral toxicity test with

Page 16 of 48bobwhite quail for desm edipham (LD 50 > 2

, 000 mg a.i./kg

- diet; MRID 41607004). In the subacute dietary studies with bobwhite quail and mallard duck, no mortality was observed at ≥5,688 mg a.i./kg

- diet , however , reduced body weight gain and food consumption were observed (at ≥2,9 28
and 5

, 688 mg a.i./kg

- diet for mallard duck (MRID 40104501) and bobwhite quail (MRID 40104502) , respectively).

No treatment

- related reproductive effects were observed in the reproduction study with bobwhite quail for phenmedipham (NOAEC = 1

, 200 mg a.i ./kg

- diet ; MRID 44862703 ). A chronic reproduction study with mallard ducks was not available for phenmedipham. For desmedipham, the chronic mallard duck study NOAEC was 90 mg a.i./kg

- diet (MRID 43544902 )

. A statistically significant 7.5% reduction in egg s hell thickness was observed at 450 mg a.i./kg

- diet. Also, the
DER considered a non

- statistically significant reduction in the percent of viable embryos (93% for
control vs. 86% at 450 treatment) and reduction in male body weight along with observed clinical signs of toxicity (walking on toes) to be treatment

- related at 450 mg a.i./kg

- diet

.

No acute passerine bird toxicological data are available. Although no mortality was observed in the acute oral and dietary studies with bobwhite and mallard, subl ethal effects of reduced body weight gain and food consumption were observed in both the mallard and bobwhite subacute dietary studies. At t he maximum application rate of 0.9 75 lbs a .i. /A

, the upper bound Kenaga residue estimates on short grass (234 mg a. i./kg) are less than 1 / 10 the highest concentration tested or at levels where effects on body weight and food consumption were observed in the sub acute dietary studies. Therefore, a n avian acute oral study using a passerine species is not requested.

M ammalian toxicity data suggest that phenmedipham (TGAI) is practically non

- toxic to small
mammals on an acute oral basis (rat LD 50 >8,000 mg / kg bw ; MRID 00067579 & 00076497 ). I n a 2

- generation reproductive toxicity study in rats, t he lowest NOAEL was reported as 75 mg a.i. /kg
bw / day , based on decreased pup body weights and body weight gains; the LOAEL was 225 mg a.i. / kg /bw/d ay ( 44862702 & 45316801 )

.

Acute contact toxicity data to bees for phenmedipham are not available. However, acute toxicity
da ta for adult honeybees are available for desmedipham, and the acute oral and contact LD 50 value s

are >50 μg a.i./bee (MRID 41711402 )

. C hronic toxicity data are not available for adult bees n or

are acute or chronic data available for larval bees

. Data on p ollinator toxicity is required to sufficiently evaluate risk to pollinators (USEPA 2014 a )

. Therefore, a cute and chronic toxicity data for honeybee larvae and chronic toxicity data for adult honeybees using parent phenmedipham
are recommended. Pending the results from the acute and chronic adult and larval honeybee studies, additional honeybee toxicity data may be necessary (semi

- field, field, pollen and nectar residue studies). Toxicity data for the degradate, MH PC are not available , however, there is no information available to suggest that MHPC is more toxic to terrestrial invertebrates than parent phenmedipham

.

No terrestrial animal toxicity data are available for MH PC , however, because the parent is practically non

- toxic on an acute basis and the degradate data for aquatic animals suggests that it is less toxic than the parent, additional toxicity data with MH PC is not requested

.

Page 17 of 48Terrestrial p lant seedling emergence and vegetative vigor data are available for phenmedipham and consists of Tier II studies using a TEP that contained both phenmedipham and desmedipham. It is noted that this formulation is no longer currently registered for use. The results of the seedling emergence and vegetative vigor studies showed that dry weight of both monocots and dicots were sensitive to treatment, with dicots exhibiting the greater sensitivity in both tests. The EC 25 values for the most sensitive monocot and dicot species from both the seedling emergence (the monocot
wheat EC 25 = 1.16 l b a.i./A , the dicot lettuce EC 25 = 0.187 lb a.i./A ; MRID 46168001 ) and vegetative vigor (the monocot onion EC 25 = 0.205 lb a.i./A, and dicot carrot EC 25 = 0.169 lb a.i./A ; MRID 46157701 ) studies were used to evaluate effects of phe n medipham exposures to n on

- target terrestrial plants

.

Table 5 . Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for Phenmedipham
Taxonomic Group Study Type Tested Species Toxicity
Value Acute Toxicity
Classification Source (Study Classification)
Comments

Birds 1 Acute Mallard Duck ( Anas platyrhynchos ) 21

- D
LD50 >
2150 mg

a .i. /kg

- bw 2 Practically non

toxic 40623501 ( Supplemental ) No mortality or
sublethal effects in the bobwhite study.

Sub

- acute dietary Bobwhite quail ( C. virginianus)
& Mallard duck ( A. platyrhynchos) 8

- D LC50

≥ 5688 mg

a .i. /kg

- diet Practically non

toxic 40104501 & 40104502 (Supplemental)

No treatment

- related mortality. Food consumption and body weight was reduced in
both studies.

Chronic Bobwhite quail ( C. virginianus ) NOAEC =
1200 mg

a .i. /kg

- diet
LOAEC > 1200 mg

a. i ./kg

- diet N/A 44862703 (Supplemental) No

treatment

- related effects
observed

Mallard duck ( A. platyrhynchos ) NOAEC =
90 mg

a .i. /kg

- diet
LOAEC =
450

a. i ./kg

diet 3 N/A 4 3544902 ( A cceptable) Endpoints affected: eggshell thickness, viable embryos, clinical signs, male body wt

Mammals Acute Oral Laboratory rat ( Rattus norvegicus ) LD 50

> 8 000 mg

a .i. /kg

- bw Practically non

toxic 00067579 & 00076497 ( A cceptable)

No mortality

.

Page 18 of 48Table 5 . Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for Phenmedipham
Taxonomic Group Study Type Tested Species Toxicity
Value Acute Toxicity
Classification Source (Study Classification)
Comments

Acute
Inhalation No Data (Study waived 1/15/88) -- N/A N/A

Chronic Laboratory rat 2

- gen NOAEC = 75 mg

a i /kg /day
LOAEC =
225 mg

a i /kg /day N/A 4 4862702 & 45316801 ( A cceptable)
Parental NOAEL: 75 mg/kg/day (achieved dosage 73.1/77.5 [M/F] mg/kg/day)

Parental LOAEL: 225 mg/kg/day (achieved dosage 211.5/242.4 [M/F] mg/kg/day),
based on decreased body weight in males (7

- 13%) and decreased body weight (9

- 15%), body weight gain (14%) and food efficiency (16%) in females

Reproductive/offsprin

g toxicity NOAEL: 75 mg/kg/day (achieved 81.4/87.6 mg/kg/day [M/F]

Reproductive/offsprin g toxicity LOAEL: 225 mg/kg/day (achieved 249.4/268.1 mg/kg/day [M/F]), based on significant decreased pup body weight (15

- 19%) and body weight gain (10

- 22%).

Insects A cute

contact Honey bee ( Apis mellifera L. ) 48

- Hr

LD 50 > 50

μg a. i

. /bee
NOEC =
36 μg

a. i

. /bee 3 Practically non

toxic 4 1711402 (Acceptable)

Page 19 of 48Table 5 . Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for Phenmedipham
Taxonomic Group Study Type Tested Species Toxicity
Value Acute Toxicity
Classification Source (Study Classification)
Comments

Acute Oral Honey bee ( Apis mellifera L. ) 48

- Hr

LD 50 > 50

μg a. i

. /bee
NOEC =
36 μg

a. i

. /bee 3 NA 4 1711402 (Acceptable)

Chronic
10

- Day Honey bee ( Apis mellifera L. ) No Data N/A N/A

Larval Emergence Honey bee ( Apis mellifera L. ) No Data N/A N/A

Terrestrial plants Seedling Emergence Dicot

– lettuce

Lactuca sativa 21

- D IC 25

= 0.187 lbs
ai /acre
NOAEC = 0.125 lbs

a i /acre 4 N/A

46168001 ( Acceptable)

Monocot

– wheat ( Triticum
aestivum ) 21

- D IC 25

= 1.16 lbs

a i /acre
NOAEC =
0.125 lbs
ae/acre 4 N/A

Vegetative vigor Dicot

— Carrot ( Daucus carota ) 21

- D IC 25

= 0.169 lbs
ai /acre
NOAEC = 0.125 lbs

a i /acre 4 N/A

46157701 ( Acceptable)

Monocot

— Onion ( Allium cepa ) 21

- D IC 25

= 0.205 lbs

a i /acre
NOAEC =
0.125 lbs
ae/acre 4 N/A

1 Birds represent surrogates for terrestrial

- phase amphibians and reptiles.

2 A split

- dosing method was used whereas the 2100 mg a.i ./kg

- bw dose was split into two equal portions with one dose given in the morning and the second dose later in the afternoon.

3 Based on toxicity data for desmedipham

4 Based on a formulation that contained both phenmedipham and desmedipham

A review of the Ecological Incident Information System (EIIS, version 2.1) and the Avian Monitoring Information System (AIMS) was completed on January 14, 2015

. There are three reported incident in EIIS for phenmedipham (described below)

. The rep orted in cident s in EIIS

Page 20 of 48indicated effects on non

- target terrestrial plants (crop damage) and the likelihood of the effects being caused by phenmedipham was considered probable and one was reported as from a registered use and the other two were from undetermined uses

. No ecological incidents involving phenmedipham were identified in AIMS (accessed January 14, 2015)

. In addition to the incident
recorded in EIIS , additional incidents have been reported to the Agency in aggregated incident reports. Pesticide registra nts report certain types of incidents to the Agency as aggregate counts of incidents occurring per product per quarter. Ecological incidents reported in aggregate reports include those categorized as ‘minor fish and wildlife’ (W

- B), ‘minor plant’ (P

- B), an d ‘other

non

- target’ (ONT) incidents. ‘Other non

- target’ incidents include reports of adverse effects to
insects and other terrestrial invertebrates. For phenmedipham , registrants have reported 0 minor fish and wildlife, 2 minor plant, and 0 other non

- tar get incidents

. Additionally, there were two reported incidents to domestic animals, where one was a fatality. Incident databases will be reviewed again at the time of the risk assessment.

Two incidents occurred in 2002 in Richmond, Montana ( I 013246

- 041 and I 013246

- 042), both involving the use of Progress (containing desmedipham, phenmedipham and ethofumesate) on

sugar beets. In the first, a ground broadcast application on June 20 probably caused stunting of all 600 acres of treated sugar beets ( I 013246

- 0 41) and 500 of 1000 acres of treated sugar beets ( I 013246

- 042). In both cases the primary probable cause was listed as "adjuvant" but the report was unclear as to the identity of the adjuvant. All three pesticide active ingredients were listed as probable. The application rate was 8 oz/A and the legality of use was listed as undetermined in
both cases. It should be noted that the label instructions stated that use of the herbicide may cause temporary growth retardation ( n ormal growth is expected to resume after 10 days )

.

In January, 2006 in Fresno, California, (I07162

- 007) a grower applied a higher rate of Progress (containing phenmedipham, desmedipham and ethofumesate) than was recommended for the crop stage, but not exceeding the maximum label rate. Flow able concentrate was applied by
broadcast at a rate of 2 pints/A. Yellowing and stunting were seen in 100% of the treated beet crop. Phen medipham was listed as a probable cause of damage to 70 acres of beets from a registered use (though the legality issue was unclear due to the higher

- than

- recommended rate).

Overall, the incident data that are available indicate that exposure pathways for phen medipham

are complete and that exposure levels are sufficient to result in field

- observable effects to non

target terrestrial plants.



## 7

. Exposure Pathways of Concern

The environmental fate properties and use patterns of phenmedipham indicate runoff

, drift , and leaching from phenmedipham applications represent potential transport mechanisms of phenmedipham to aquati c and terrestrial organisms.

The d rinking water exposure pathway for birds and mammals w as screened using the SIP (Screening Imbibition Program) screening method

. The inhalation exposure pathway is typically evaluated using the STIR (Screening Tool for Inhalation Risk) screening method. SIP and STIR
are described in detail at: http://www.epa. gov/oppefed1/models/terrestrial/index.htm

. T he drinking water pathway alone for phenmedipham was found to not be an exposure pathway of

Page 21 of 48potential concern. SIP results are presented in Appendix C

. The inhalation exposure pathway
could not be evaluated usi ng STIR as a result of the lack of mammalian inhalation data. However, due to the low vapor pressure ( 9.75 x 10

- 12 mmHg), the inhalation exposure pathway is not considered likely to be an exposure pathway of potential concern.



## 8

. Analysis Plan

**8.1 Stressors of Concern** 

8.1.1 Ecological Risk

The stressor of ecological concern for terrestrial and aquatic organisms is the parent compound, phenmedipham

.

8.1.2 Drinking Water

The Health Effects Division ( HED ) Metabolism Committee ( MARC ) determined that the residue of concern in drinking water is phenmedipham per se (Memo, 06/07/2001, W. Donovan, et al., D275136). The refore, the chemical that will be assessed in drinking water from surface and ground water is th e parent compound only

.

Expected drinking water concentrations (EDWC) for the spinach and table beet uses will be
modeled during registration review , due to the introduction of new (PRZM

- GW) or revised (SWCC) models since the last assessment.



### 8.2 **Measures of Exposure**

8.2.1 Modeling of Ecological Exposure

EFED will use standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm

.

8.2.2 Modeling of Drinking Water in Human Dietary Risk Assessment

The drinking water assessments conducted to support future human health risk assessments of phenmedipham will incorporate modeling of phenmedipham in surface and ground water. Since the last drinking water assessment was conducted, EFED has updated its surface and ground water models, the drinking water modeling input parameters, and the percent crop ped area (PCA) guidelines. Through the course of the phenmedipham registration review, the Agency will determine whether a revised drinking water assessment will need to be conducted. For all modeling, input parameters are selected according to the current input guidelines, and wh ere in question a conservative approach is taken in the selection of half

- lives. Descriptions of all

Page 22 of 48executable versions of current models for drinking water exposure can be obtained from the following URL link: http://www.epa.gov/oppefed1/models/water/

8.2.3 Available Water Quality Monitoring Data

EFED will consider all ground and surface water monitoring data available to us, and will conduct a comprehensive evaluation of the data for the risk assessment. The data that may be considered include the United States Geological Survey (USGS) National Water

- Quality Assessment (NAWQA) Program monitoring data , and any State data available at the time of risk

assessment

.



### 8.3 **Measures of Effect**

Toxicity data presented in Section 6 of this problem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk assessment will be considered. The open literature studies are
iden tified using EPA’s ECOTOXicology database ( ECOTOX) (USEPA, 2007), which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insi ght into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the affected
communities.



## 9. Endangered Species Assessmen t

Consistent with EPA’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of pesticides in accordance with the Joint Interim Approaches developed to implement the recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing
Risks to Endangered and Threatened Species from Pesticides

. The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA. EPA will address concerns specific to phenmedipham in connection with the development of its final registration review decision for phenmedipham

.

In No vember 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the Services), and USDA released a white paper containing a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the NAS recommendations, and reflect a common approach to risk ass essment shared by the agencies as a way of addressing scientific
differences between the EPA and the Services. Details of the joint Interim Approaches are contained in the November 1, 2013 white paper

, Interim Approaches for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report.

Page 23 of 48Given that the agencies are continuing to develop and work toward implementation of t he Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, this ecological problem formulation supporting the Preliminary Work Plan for phenmedipham does not describe the specific ESA analysis , including effects determinations for specific listed species or designated critical habitat, to be conducted during registration review. While the agencies continue to develop a common method for ESA analysis, the planned risk assessment for the registr ation review of phenmedipham will describe the level of ESA analysis completed for this particular registration review case. This assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists, once the scientific methods being developed by the agencies have been fully vetted. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses of phenmedipham as part of completing this registration review

.



## 10. Endocrine Disruptor Screening Program

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

outco mes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpo ints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecologica l hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of the Problem Formulation for Registration Review for phenmedipham

, EPA reviewed these d ata and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), phenmedipham is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlif e similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and
establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list

Page 24 of 48of chemicals identified for EDSP screening was published on June 14, 2013 1 and includes some pesticides scheduled for registrat ion review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, t he test guidelines and the Tier 1 screening battery, please visit our
website. 2



## 11

. Preliminary Identification of Data Gaps

**11.1 Environmental Fate** 

Table 6 identifies environmental fate studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data for phenmedipham
acid are needed to support the risk assessment

.

Table 6

. Available envi ronmental fate data for phenmedipham and remaining data gaps.

158
Guideline (OPPTS) Description MRID Classification Data Gap? Comments

835.1240

(163

- 1)

Adsorption/ Desorption 00142747
00142749
40765701
40765702
42099102
46286301
46286303 Supplemental No

--

835.2120

(161

- 1) Hydrolysis 40502708 Acceptable No

--

835.2240

(161

- 2) Photodegradation
in Water 42429901 Acceptable No

--

835.2410

(161

- 3) Photodegradation
on Soil 00142742 Supplemental No

--

835.4100

(162

- 1) Aerobic Soil
Metabolism 00142744 Supplemental No Need U.S. classification of foreign
soils used

835.4200

(162

- 2) Anaerobic Soil
Metabolism 42099101
42990301 Acceptable No

--

1 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.

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

Page 25 of 48Table 6

. Available envi ronmental fate data for phenmedipham and remaining data gaps.

158
Guideline (OPPTS) Description MRID Classification Data Gap? Comments

835.4300 (162

- 4) Aerobic A quatic
metabolism 46302501 Supplemental No Need U.S.
classification of foreign
sediment used

835.4400 (162

- 3) Anaerobic Aquatic
Metabolism -- -- No Data not needed for
risk assessment

835.6100 (164

- 1) Terrestrial Field Dissipation 42891601
46412301
46412302 Supplemental No

--

850.6100 Environmental Chemistry
Method: Soil
&Water Yes

850.1730

(165

- 4) Fish
Bioconcentration

Factor 40912801 Acceptable No

--



### 11. **2 Effects** 

Tables 7 and 8 identify ecological effects studies by MRID that offer data for each guideline requirement, as well as study classifications and whether or not further data are needed in order to support risk assessment. Data call

- in justifications are presented in Appe ndix D.

Table 7 . Available ecological effects data for aquatic organisms exposed to phenmedipham and remaining data gaps.

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classification Are data
needed to
conduct
risk
assessment? Justification and Assumptions
EPA will Make in Absence of
Data

850.1010 Freshwater
invertebrate acute toxicity 45414201
00116712 Invalid Supplemental 1 No

850.1025
850.1035
850.1045
850.1055 Saltwater
invertebrate acute toxicity 4 8587107 Acceptable 1 No

Page 26 of 48Table 7 . Available ecological effects data for aquatic organisms exposed to phenmedipham and remaining data gaps.

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classification Are data
needed to
conduct
risk
assessment? Justification and Assumptions
EPA will Make in Absence of
Data

850.1075 Freshwater
fish acute toxicity 00116336/
02770201 Invalid No

0011633 7 /
02770201 Invalid

00116713 Supplemental 1

00116714 Supplemental 1

850.1075 Saltwater fish acute toxicity No data N/A No No studies have been submitted. Exposure is estimated to be low

. P arent and degradate toxicity
data with freshwater fish indicate degradate is less toxic.
Substantial differences in toxicity between freshwater fish
and estuarine/marine fish are not anticipated. EFED will us e available freshwater fish toxicity
data unless additional data is
available.

850.1300 Freshwater
invertebrate life cycle No No studies have been submitted. Chronic exposure is anticipated to be primarily from degradate,
MHCP. Based on acute
fres hwater invertebrate MHCP toxicity data (slightly toxic), chronic toxicity values are anticipated to be substantially greater than the EECs. Additional open literature
chronic freshwater invertebrate toxicity data are available and
EFED will use this data u nless
additional data is available.

Page 27 of 48Table 7 . Available ecological effects data for aquatic organisms exposed to phenmedipham and remaining data gaps.

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classification Are data
needed to
conduct
risk
assessment? Justification and Assumptions
EPA will Make in Absence of
Data

850.1350 Saltwater
invertebrates life cycle No data N/A No No studies have been submitted. Chronic exposure is anticipated to be primarily from degradate,
MHCP. Based on acute
freshwater invertebrate MHCP toxicity data (slightly toxic), chronic toxicity values are anticipated to be substantially greater than the EECs. EFED
will also use the toxicity data
from the available freshwater invertebrate life cycle study as
the chronic saltwater invertebrate endpoint unles s additional data is
available.

850.1400 Freshwater
fish early

- life
stage No data N/A No No studies have been submitted. Chronic exposure is anticipated to be primarily from degradate, MHCP and degradate toxicity
data with freshwater fish indicate degradate is less toxic. EFED
will use available freshwater fish

acute toxicity data and predicted
chronic values unless additional
data is available.

850.1400 Saltwater fish early

- life
stage No data No No studies have been submitted. Chronic exposure is anticipated to be primarily from degradate,

MH PC and degradate toxicity
data with freshwater fish indicate degradate is less toxic

. Substantial differences in toxicity between freshwater fish
and estuarine/marine fish are not anticipat ed. EFED will use available freshwater fish toxicity
data unless additional data is
available.

Page 28 of 48Table 7 . Available ecological effects data for aquatic organisms exposed to phenmedipham and remaining data gaps.

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classification Are data
needed to
conduct
risk
assessment? Justification and Assumptions
EPA will Make in Absence of
Data

850.1500 Fish life cycle No data No Data have not been submitted to fulfill this guideline. A data gap
was not identified as these data
are not necessary for risk
assessment at this time.

850.1735 Whole
Sediment
Acute Toxicity Invertebrates,
Freshwater No data N/A Yes Phe n medipham may partition to soil/sediment and therefore, sediment organisms may be exposed. The exposure should
be from treated sediment and not overlying water.

850.1740 Whole
Sediment
Acute Toxicity Invertebrates,
Saltwater No data N/A Yes Phe n medipham may partition to soil/sediment and therefore, sediment organisms may be exposed. The exposure should
be from treated sediment and not overlying water.

850.4400 Aquatic plant Toxicity Test using Lemna

spp. 43053505 Acceptable 1 No

850.4500 Algal toxicity 43053504 Acceptable 1 No

43053501 Acceptable 1

43053503 Acceptable 1

44909602 Supplemental

850.4550 Cyanobacteria 43053502 Acceptable No

1 Based on toxicity data for desmedipham

Page 29 of 48Table 8 . Available ecological effects data for terrestrial organisms exposed to phenmedipham and remaining data gaps.

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are data
needed for
risk
assessment? Justification and Assumptions EPA
will Make in Absence of Data

850.2100 Avian oral toxicity 40623501 Supplemental No An acute oral study with a passerine species has not been submitted to the

agency. However, the expected
maximum EECs are not greater than 1/10 the highest application rate tested
in the avian acute studies where
sublethal effects were observed. 4 1607004 Acceptable 1

850.2200 Avian dietary toxicity 00115879/
27701207 Invalid No

0015850 Invalid

40104501 Supplemental

40104502 Supplemental

850.2300 Avian reproduction 44862703 Supplemental No

43544902 Acceptable 1

Non

guideline Avian
inhalation No Data N/A No Data have not been submitted to fulfill this guideline. A data gap was not
identified as these data are not necessary for risk assessment at this
time.

850.3020 Honey bee

acute contact toxicity 41711402 Acceptable No

850.3030 Honey bee
residue on foliage No Data N/A No Data have not been submitted to fulfill this guideline. A data gap was not
identified based on the adult acute
contact data

. Non

guideline Honey bee
adult acute oral toxicity 41711402 Acceptable No

Page 30 of 48Table 8 . Available ecological effects data for terrestrial organisms exposed to phenmedipham and remaining data gaps.

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are data
needed for
risk
assessment? Justification and Assumptions EPA
will Make in Absence of Data

Non

guideline Honey bee
adult chronic oral toxicity No Data N/A Yes Chronic (repeated dose) data is needed on adult honey bees to evaluate chronic risk to pollinators for the risk assessment. Although EPA has not developed a guideline for this study, guidance for a 10

- day oral toxicity study is currently in d evelopment by
OECD. A protocol should be submitted prior to study initiation. Study should be conducted with phenmedipham acid.

Non

guideline Honey bee
larval acute oral toxicity No Data N/A Yes In addition to the adult honey bee data gaps identified above, data is needed for the additional honey bee life stage of larvae to complete the risk assessment for pollinators. Although EPA has not developed a guideline for these studies, OECD TG237 may b e used to assess acute oral effects on larvae. Chronic (repeat dose) study guidance for assessing chronic oral toxicity to honey bee larvae is currently in development by OECD. A protocol should be submitted prior to study initiation. Study should be con ducted using phenmedipham acid. Non

guideline Honey bee
larval chronic oral toxicity No Data N/A Yes

Non

guideline Semi

- field testing for pollinators (tunnel or colony feeding studies) No Data N/A Pending Data have not been submitted to fulfill
this guideline. Results from lower tier
studies should inform the conduct of the field test to address remaining uncertainties. Pending the results of lower tier studies (adult honey bee acute oral, chronic adult honey bee, acute and chronic larval), a field t esting study may not be needed to complete the risk assessment for pollinators. A protocol should be submitted prior to
test initiation

Page 31 of 48Table 8 . Available ecological effects data for terrestrial organisms exposed to phenmedipham and remaining data gaps.

OCSPP
Guideline Data Requirement Submitted
Studies (MRID) Study
Classifications Are data
needed for
risk
assessment? Justification and Assumptions EPA
will Make in Absence of Data

Non

guideline Field trial of
residues in pollen and

nectar No Data N/A Pending Data have not been submitted to fulfill this guideline. Results from lower tier
studies should inform the conduct of the field test to address remaining uncertainties. Pending the results of lower tier studies (adult honey bee acute oral, chronic adult honey bee, acute and chronic larval), a fi eld testing study may not be needed to complete the risk assessment for pollinators. A protocol should be submitted prior to
test initiation

850.3040 Field testing
for pollinators No Data N/A Pending Data have not been submitted to fulfill this guideline. Results from lower tier
studies should inform the conduct of the field test to address remaining uncertainties. Pending the results of lower tier studies (adult honey bee acute oral, chronic adult ho ney bee, acute and chronic larval), a field testing study may not be needed to complete the risk assessment for pollinators. A protocol should be submitted prior to
test initiation.

850.3100 Earthworm
Subchronic Toxicity Test None N/A No Data have not been submitted to fulfill this guideline. A data gap was not
identified as these data are not necessary for risk assessment at this
time.

850.4100 Seedling Emergence and Seedling
Growth 46168001 Acceptable No

850.4150 Vegetative Vigor 46157701 Acceptable No

Page 32 of 48

## 12. References

USEPA. 1980. Ambient Water Quality Criteria for Isophorone. Office of Water Regulations and Standards Criteria and Standards Division. Washington D.C. EPA 440/5

- 80

- 056. October 1980.

USEPA. 2005. EFED Scien ce Assessment for the Reregistration Eligibility Decision (RED) Document for Case 02777: Phenmedipham. Office of Pesticide Programs. Environmental Fate and Effects Division. March 31, 2005. DP306158.

USEPA. 2011. Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments in Support of the Registration Review of Desmedipham. Office of Pesticide Programs, Environmental Fate and Effects Di vision. June 27,
2011. DP 384772.

USE PA. 2014. BEAD Chemical Profile for Registration Review: Phenmedipham (098701). Office of Pesticides Program, Biological and Economic Analysis Division. Arlington, VA.

USEPA. 2014a. Guidance for Assessing Pesticide Risks to Bees. Office of Pesticide Programs, USEPA, Washington D.C. Health Canada Pest Management Regulatory Agency, Ottawa, ON, Canada. California Department of Pesticide Regulation, Sacramento, CA. June 23, 2014.

Vidal, T., N. Abrantes, A. M. M. Gonca lves and F. Goncalves. 2012. Acute and c hronic t oxicity
of Betanal® e xpert and i ts a ctive i ngredients on n ontarget a quatic o rganisms from d ifferent

t rophic l evels. Environ. Tox . 27(9): 537

- 548.

USEPA, 2001 a

. Phenmedipham . Results of the Health Effects Division (HED ) Metabolism
Assessment Review Committ ee (MARC) Meeting Held on 22

- MA Y

- 2001. Chemical#s 128943
& 129041. Barcode D275136. Case 291904. Submission 8581930. Office of Pesticides Program,
Health Effects Division, Arlington, VA. J une 7, 2001.

Page 33 of 48

### A **ppendix A. Available**  **Toxicity Data for Phen**  **medipham and**
**Des medipham** 

Comparison of toxic profiles of Phenmedipham and Desmedipham

Test Des medipham Endpoint/Toxicity Classification Study Classification/ Study MRID Phen medipham Endpoint/Toxicity Classification Study Classification/ Study MRID
Acute fish toxicity LC50 (rainbow trout) 1.7 mg a.i./L/ moderately toxic Supplemental/ 00116714 No data (submitted study was invalid)

MHPC

– 74.1 mg a.i./L/ Slightly toxic Supplemental/ 45414203
Acute fish toxicity LC50 ( bluegill
sunfish ) 6.0 mg a.i./L/ moderately toxic Supplemental/ 00116713 Parent

- No data (submitted study was invalid)

Acute
freshwater
invertebrate toxicity EC50 1.88 mg a.i./L/ moderately toxic Supplemental/ 00116712 Parent

- No data (submitted study was invalid)

MHPC

– 14 mg a.i./L/ Slightly toxic Supplemental/ 45414202

Acute
estuarine/marine
invertebrate toxicity LC50 1.2 mg a.i./L/ moderately toxic Acceptable/ 48587107 No data submitted

Avian Acute toxicity LD50 >2000 mg/kg

- bw (bobwhite quail) / Practically non

- toxic Acceptable/41607004 >2100 mg/kg

- bw (mallard) / Practically

non

- toxic Supplemental/ 40623501
Avian Subacute Dietary LC50 >5000 mg/kg

- diet (bobwhite quail & mallard duck) / Practically non

- toxic Acceptable / 0011411 1 & 00114112 >5 688 & >5790 mg/kg

- diet (bobwhite quail & mallard duck)/ Practically non

toxic Acceptable / 40104501 & 40104502
Avian Reproduction (bobwhite quail)
NOAEC NOAEC/LOAEC = 450/2500 mg/kg

- diet Acceptable / 43544901 NOAEC/LOAEC = 1200/ >1200 mg/kg

- diet Acceptable / 44862703

Avian Reproduction (mallard duck)
NOAEC NOAEC/LOAEC = 90/450 mg/kg

- diet Acceptable / 43544902 No data submitted

Acute
Mammalian toxicity LD50 (rat) >5000 mg/kg

- bw / Practically non

- toxic Acceptable / 00155581 >8000 mg a.i ./kg

- bw / Practically non

toxic Acceptable / 00067579 & 00076497

Mammalian Reproduction (rat) NOAEC/LOAEC = 4/20 mg/kg

- bw Acceptable / 40387105 NOAEC/LOAEC = 75 /225 mg ai/kg/day Acceptable / 44862702

Page 34 of 48Acute adult honeybee contact toxicity
LD50 >50 μg a.i ./bee / Practically non

- toxic Acceptable / 41711402 No data submitted

Acute adult honeybee oral toxicity LD50 >50 μg a.i./bee / Practically non

- toxic Acceptable / 41711402 No data

Aquatic non

vascular plant toxicity
IC50/NOAEC IC50/NOAEC = 0.14/<0.12 mg a.i./L (diatom) Acceptable / 43053503 IC50/NOAEC = >13/<0.18 mg a.i./L (green algae) Acceptable / 44909602

Aquatic vascular plant toxicity
IC50/NOAEC IC50/NOAEC = >1.02/1.02 mg a.i./L Acceptable / 43053505 No data submitted

Terrestrial Plant

– Seedling Emergence
IC25/NOAEC IC25/NOAEC = 0.31/0.15 lb a.i./A (tomato) Acceptable / 42366302 IC25/NOAEC = 0.187/0.125 lb a.i./A (lettuce) Acceptable / 46168001

Terrestrial Plant

– Veg Vigor
IC25/NOAEC IC25/NOAECL = 0.13/<0.10 lb a.i./A (carrot) Acceptable/ 460802 01 IC25/NOAECL = 0.169/0.125 lb a.i./A (carrot) Acceptable/ 46157701

Page 35 of 48

### Appendix B

**. Predictive Data for Parent**  **Phenmedipham and its**  **Degradates from QSAR Modeling using Ecosar v1.11**

Parent Phenmedipham

ECOSAR Version 1.11 Results Page

SMILES : O=C(Oc1cccc(c1)NC(=O)OC)Nc2cc(ccc2)C

CHEM :

CAS Num:
ChemID1:

MOL FOR: C16 H16 N2 O4

MOL WT : 300.32 Log Kow: 3.274 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: 3.59 (PhysProp DB exp value

- for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: 143.00 (deg C, PhysProp DB exp value for Wat Sol est) Wat Sol: 4.961 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: 4.7 (mg/L, Phys Prop DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 3.274 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 4.7 (mg/L, PhysProp DB exp value)

-------------------------------------- ECOSAR v1.11 Class

- specific Estimations

-------------------------------------- Carbamate Esters Carbamate Esters, Phenyl
Predicted

ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Carbamate Esters : Fish 96

- hr LC50 4.922 * Carbamate Esters : Daphnid 48

- hr LC50 4.265 Carbamate Esters : Green Algae 96

- hr EC50 0.183
Carbamate Esters : Fish ChV 0.516 ! Carbamate Esters : Daphnid ChV 0.662 ! Carbamate Esters : Green Algae ChV 2.308

Carbamate Esters, Phenyl : Fish 96

- hr LC50 2.655 Carbamate Esters, Phenyl : Daphnid 48

- hr LC50 0.00184

Carb amate Esters, Phenyl : Green Algae 96

- hr EC50 1.119 Carbamate Esters, Phenyl : Fish ChV 0.155 Carbamate Esters, Phenyl : Daphnid ChV 0.004 Carbamate Esters, Phenyl : Green Algae ChV 0.294

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 17.694 * (Baseline Toxicity) : Daphnid 48

- hr LC50 11.301 * : Green Algae 96

- hr EC50 13.692 *
: Fish ChV 1.987 : Daphnid ChV 1.529

Page 36 of 48: Green Algae ChV 4.660

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the
water solubil ity by 10X, typically no effects at saturation (NES) are reported.

NOTE: ! = exclamation designates: The toxicity value was estimated through application of acute

- to

- chronic ratios per methods outlined in

the ECOSAR Meth odology Document provided in the ECOSAR Help Menu.

------------------------------ Class Specific LogKow Cut

- Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut

- offs presented below, then no effec ts at saturation are expected for those endpoints.

Carbamate Esters :

----------------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Carbamate Esters, Phenyl:

------------------------ Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

----------- -------------------------------------------------------------------

MH PC

ECOSAR Version 1.11 Results Page

SMILES : c1(cc(ccc1)O)NC(=O)(OC)

CHEM :

CAS Num:
ChemID1:

MOL FOR: C8 H9 N1 O3

MOL WT : 167.17 Log Kow: 0.920 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: (PhysProp DB exp value

- for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate)

Wat Sol: 1.038E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Wat Sol: (User Entered) Wat Sol: (PhysProp DB exp value)

Page 37 of 48-------------------------------------- Values used to Generate ECOSAR Profile

------------------------------------- - Log Kow: 0.920 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 1.038E+004 (mg/L, EPISuite WSKowwin v1.43 Estimate)

-------------------------------------- ECOSAR v1.11 Class

- specific Estimations

-------------------------------------- Phenols

Carbamate Esters Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Phenols : Fish 96

- hr LC50 192.110 Phenols : Daphnid 48

- hr LC50 35.765 Phenols : Green Algae 96

- hr EC50 182.690
Phenols : Fish ChV 16.557 Phenols : Daphnid ChV 6.816 Phenols : Green Algae ChV 87.007 Phenols : Fish (SW) 96

- hr LC50 105.565

Phenols : Earthworm 14

- day LC50 429.137 Phenols : Lemna gibba 7

- day EC50 179.659

Carbamate Esters : Fish 96

- hr LC50 142.760

Carbam ate Esters : Daphnid 48

- hr LC50 122.480 Carbamate Esters : Green Algae 96

- hr EC50 0.375
Carbamate Esters : Fish ChV 14.781 !

Carbamate Esters : Daphnid ChV 13.859 ! Carbamate Esters : Green Algae ChV 17.267

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 1280.371 (Baseline Toxicity) : Daphnid 48

- hr LC50 658.027 : Green Algae 96

- hr EC50 324.598
: Fish ChV 111.2 68 : Daphnid ChV 48.625 : Green Algae ChV 68.083

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predic ted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

NOTE: ! = exclamation designates: The toxicity value was estimated through application of acute

- to

- c hronic ratios per methods outlined in the ECOSAR Methodology Document provided in the ECOSAR Help Menu.

------------------------------ Class Specific LogKow Cut

- Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut

- offs presented below, then no effects at saturation are expected for those endpoints.

Phenols:

------- Maximum LogKow: 7.0 (Fish 96

- hr LC50, Daphnid LC50) Maximum LogKow: 6.4 (Earthworm, Lemna)

M aximum LogKow: 7.0 (Green Algae EC50 Maximum LogKow: 8.0 (ChV)

Page 38 of 48Maximum LogKow: 5.0 (Fish (SW) 96

- hr LC50, Mysid)

Carbamate Esters :

----------------- Maximum LogKow: 5.0 (LC50) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)

------------------------------------------------------------------------------

All values are in ppm ND = No empirical Data NP = No prediction made for this class.

Red highlighted cells indicate poor agreement ( i.e. > 10x difference) between empirical data and predicted values.
Yellow highlighted cells indicate reasonable agreement ( i. e. between 5x and 10x difference) between empirical data and predicted values.
Green highlighted cells indicate good agreement ( i.e. <5x difference) between empirical data and predicted values.

The empirical EC 50 for green algae was nondefinitive with no effects found at the dose of >13 mg/L . However, since the level of predicted toxicity is approximately 10

- 100 times lower than
the tested doses (except for the baseline toxicity class of neutral organic) , it is unclear how well
the model predicts the actual toxicity of parent phenmedipham and therefore the QSAR approach
should not be used in risk assessment to evaluate the toxicity of phenmedipham metabolites to green algae.

Green Algae EC50 Empirical
EC50 Carbamate
Esters Carbamate Esters, Pheny l Phenols Neutral Organic

Parent >13 0.183 1.12 NP 13.7

MHCP ND 0.375 NP 183 324

The predicted toxicity for the three classes vary with the non

- definitive empirical NOAEC for green algae being less than all three classes . Therefore, it is unclear how well the model predicts the actual toxicity of parent phenmedipham and therefore the QSAR approach should not be used in the risk assessment to evaluate the toxicity of phenmedipham metabolites to green algae.

Green Algae NO AEC Empirical
NOAEC Carbamate
Esters Carbamate Esters, Phenyl Phenols Neutral Organic

Page 39 of 48Parent <0.18 2.3 0.29 4.7

MHCP ND 17.3 NP 87 68

The predicted values for daphnids varied greater and were both above and below the empirical
EC50 value. Therefore , it is unclear how well the model predicts the actual toxicity of parent phenmedipham and therefore the QSAR approach should not be used in the risk assessment to evaluate the toxicity of phenmedipham metabolites to freshwater invertebrates on an acute ba sis.

Daphnid EC50 Empirical
EC50 Carbamate
Esters Carbamate Esters, Phenyl Phenols Neutral Organic

Parent 1.88 4.27 0.0018 NP 11.3

MHCP 14 122 NP 35.7 658

A NOAEC value was not available for chronic exposure to daphnids. The open literature paper by Vidal et al. 2013 reported EC50, EC20 and EC10 values with the lowest being 0.059 mg/L.

. As with the predicted acute toxicity values, the chronic values also vary and therefore are unclear in how well the model may predict actual toxicity.

Daphnid No eff ect Empirical
NOAEC Carbamate
Esters Carbamate Esters, Phenyl Phenols Neutral Organic

Parent 0.059 0.662 0.004 NP 1.53

MHCP ND 13.8 NP 6.82 48.6

There i s relatively good agreement between the modeled values and the empirical data for fish acute toxicity data. T herefore the QSAR approach could be used in the risk assessment to support the evaluate the toxicity of phenmedipham to freshwater fish on an acute basis.

Fish LC50 Empirical EC50 Carbamate
Esters Carbamate Esters, Phenyl P henols Neutral Organic

Parent 1.7 and 6.0 4.92 2.66 NP 17.7

MHCP 74 143 NP 19 2 1280

Page 40 of 48

### Appendix C **. Screening Level Models to Evaluate Potential Importance of Drinking Water and Inhalation Exposure Pathways**  **for Ecological Risk analysis** 

SIP ( Screening Imbibition Program, v1.0) Inputs and Conclusions

Non

- definitive acute toxicity LD/LC50 values used as a conservative estimate

Table 1. Inputs

Parameter Value

Chemical name phenmedipham Solubility (in water at 25 o C; mg/L) 4.7

Mammalian LD 50 (mg/kg

- bw) 8000 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 75 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

- bw) 2100 Avian test species mallard duck Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 90 Bobwhite quail NOAEC (mg/kg

- diet) 1200 NOAEC (mg/kg

- diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg

- diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Table 2. Mammalian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 0.8084 0.8084 Adjusted toxicity value (mg/kg

- bw) 6153.2845 57.6870 Ratio of exposure to toxicity 0.0001 0.0140

Conclusion* Drinking water exposure alone is NOT a potential

concern for mammals Drinking water exposure alone is NOT a potential

concern for mammals

Table 3. Avian Results

Page 41 of 48Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 3.8070 3.8070 Adjusted toxicity value (mg/kg

- bw) 1090.3734 4.4651 Ratio of exposure to acute toxicity 0.0035 0.8526

Conclusion* Drinking water exposure alone is NOT a potential
concern for birds Drinking water exposure alone is NOT a potential
concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non

- target animals.

Page 42 of 48

### Appendix **D**

**. Data Justification Tables for Non** 

**- guideline**  **Studies**

Study Title: Pollinator Acute Oral Toxicity, Larvae Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where larvae and pupae may be e xposed. Therefore, potential adverse effects to developing bees and other insect pollinators could result from exposure to pesticide residues. Available toxicity studies do not address possible effects on brood (larvae and pupae) survival/development. B ecause of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine the acute oral toxicity of this compound to bee brood.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for terrestrial invertebrates using the honeybee as a surrogate test species. The guidance discusses Tier I laboratory

- based acute toxicity studies of individual honeybee larvae as a critical compone nt of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance can be found at: http://www2.epa.g ov/pollinator

- protection/pollinator

- risk

assessment

- guidance . Additional guidance on larval honeybee toxicity test design can be found in
OECD Test Guideline 237 http://www.oecd

- ilibrary.org/environment/test

- no

- 237

- honey

- bee

- apis

mellifera

- larval

- toxicity

- test

- single

- exposure_9789264203723

- en

. Practical Utility of the Data

How will the data be used?

The Tier I acute oral toxicity d ata on honeybee larvae serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms such as federally listed threatened or endangered and non

- listed terrestrial invertebrate insects, includi ng pollinators, and/or modify their designated critical habitat from acute oral exposures to pesticides. The data will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding o f the potential effects on terrestrial species and whether there is a differential sensitivity of larval bees relative to adult bees. If acute oral effects data for larvae are not available, risks to terrestrial insects from acute oral exposure will be as sumed How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- targe t species or is likely to adversely affect listed threatened or endangered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFR A and the ESA, and could result in use restrictions.

Study Title: Pollinator Chronic Oral Toxicity, Adult Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently

Page 43 of 48brought back to the hive. Therefore, potential chronic effects to adult honeybees and other pollinators from oral exposure to some pesticides could exist. Currently available toxicity studies do not address possible lethal and sublethal effects of chronic oral exposure on adult terrestrial
invertebrates and will assist in determining whether the sensitivity of adult bees differs from that of earlier life stages. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is importan t to determine the chronic oral toxicity of this compound to adult honeybees and other pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance discusses Ti er I laboratory

- based chronic oral toxicity studies of individual adult honeybees as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance
can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Study design elements for the chronic 10

- day oral toxicity test with honeybees are similar to the OECD Test Guideline 213 acute oral toxicity test http://www.oecd

- ilibrary.org/environment/test

- no

213

- honeybees

- acute

- oral

- toxicity

- test_9789264070165

- en

. Practical Utility of the Data

How will the data be used? The Tier I chronic oral toxicity d ata on adult bees serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threatened or endangered species and non

- listed terrestrial invertebrate insects, including pollinators, from chronic oral exposures to pesticides. Th e data will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, pa rticularly insect pollinators and to determine whether adult toxicity differs substantially from other life stages evaluated in other Tier I tests. If chronic oral effects data for adults are not available, risks to
terrestrial insects from chronic oral e xposure will be assumed. How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse e ffects to non

- target species or is likely to adversely affect listed threatened or endangered species and/or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comp ly with FIFRA and the ESA, and could result in use restrictions.

Study Title: Pollinator Chronic Oral Toxicity, Larvae Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where larvae and pupae may be e xposed. Therefore, potential effects to developing bees could result from chronic oral exposure to pesticide residues. Available toxicity studies do not address possible chronic effects on brood (larvae and pupae) survival. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to
determine chronic larval/pupal toxicity and whether adult emergence is adversely affected. This study will

Page 44 of 48provide information on w hether honeybee larvae differ in sensitivity from adult bees following chronic

exposure.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance discusses Tier 1 labor atory

- based chronic oral toxicity studies of individual honeybee larvae as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information on larval honeybee toxicity repeat exposure test design can be found in the oE CD draft guidance http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.pdf

. Practical Utility of the Data

How will the data be used? The Tier I chronic oral toxicity d ata on bee larvae serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threatened or endangered and non

- listed

terre strial invertebrate insects, including pollinators, from chronic oral exposures to pesticides. The data
will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the pote ntial direct and indirect lethal and sublethal effects on a broad range of terrestrial species, particularly insect pollinators. These data will also assist in determining whether early life stages of the bee differ in their sensitivity to pesticides rela tive to adults. If chronic oral effects data for larvae are not available, risks to terrestrial insects from chronic oral exposure will be
assumed. How could the data impact the Agency’s future decision

- making? The data will inform the determination requi red under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endangered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.

Study Title: Pollinator Tier II Semi

- Field Toxicity Test ing (tunnel/enclosure studies) Rationale for Requiring the Data Tier II studies are conditional on the outcome of the screening

- level assessment where acute and/or
chronic risk levels of concern have been exceeded for terrestrial invertebrates. Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back
to the hive and may adversely affect develo ping brood (egg, larvae, and pupae) and adult bees

. Screening

- level (Tier I) studies of individual bees do not address possible effects and/or exposure to pesticide residues at the colony

- level. Because of the potential for pollen and nectar to be

contam inated with pesticide residues, and subsequently brought back to the hive, it is important to
determine whether bee colonies may be negatively affected under relatively controlled exposure
conditions of a semi

- field study. In addition to providing effects data, these studies can provide data on exposure as pesticide residues in pollen/nectar of treated plants.

Page 45 of 48The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance descr ibes the tiered testing process and can be found

at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Additional
information on ho neybee colony studies under semi

- field conditions can be found in the OECD
Guidance 75 http://www.oecd.org/officialdocuments/publicd isplaydocumentpdf/?cote=env/jm/mono%28

. Practical Utility of the Data

How will the data be used? Tier II colony

- level data will be used to assess potential risk to non

- target organisms including listed
and non

- listed terrestrial social invertebrate species and to determine whether effects observed in the screening

- level (Tier I) laboratory

- based studi es of individual bees are evident in colony

- level
studies under semi

- field conditions. The Tier II semi

- field test of whole colonies is a relatively controlled study, i.e ., bees are confined to a specific area, that is designed to represent potential
fiel d

- level exposure and account for hive dynamics, which are not achievable from other pollinator
studies. This study will be used to determine whether adverse effects to insect pollinators at the whole colony level, may result for the use of pesticides and will help to refine risk estimates derived in the screening

- level risk assessment for beneficial terrestrial invertebrates. Measured residues in pollen/nectar can also be used to refine risk estimates derived from model

- based or default values in
the scre ening

- level assessment.

How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse e ffects to non

- target species or is likely to adversely affect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products t o comply with FIFRA and the ESA, and could result in significant use
restrictions.

Study Title: Pollinator Tier II Semi

- Field Toxicit y Testing (feeding studies) Rationale for Requiring the Data

Pesticide r esidues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hiv e, and may adversely affect developing brood (egg

, larva e, and pupae ) and
adult bees

. Tier II feeding studies are conditional on the outcome of the screening

- level assessment
where acute and/ or chronic risk levels of concern have been exceeded for terrestrial invertebrates based on Tier I studies of individual bees. Feeding studies utilize free foraging bee colonies that are “dosed” with specific quantities of test material and represent a mea ns of ensuring exposure to the test material through spiked pollen and/or sugar solutions fed to the colony while still allowing the bees to forage freely. Since bee colonies are not confined to enclosures, colonies can be exposed for longer duration peri ods without subjecting the bees to stress that typically results from Tier II tunnel
studies. Available toxicity studies of individual bees (Tier 1) conducted to support screening

- level

assessments do not address possible eff ects and/or exposure to pestic ide residues at the colony

- level

. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine whether bee colonies may be negatively affected where bees are free foraging and have the option to collect/consume alternative

Page 46 of 48forage items beyond the spiked food

. Since multiple dose levels can be more readily tested, feeding studies can help to define dose

- response relationships at the whole colony level.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance describes the tiered testing process and can be found

at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Additional information on honeybee colony feeding studies can be found in the EPPO Guidance 170 at: http://www.nationalbeeunit.com/index.cfm?pageId=187

.

Practical Utility of the Data

How will the data be used? Tier II colony feeding data will be used to assess potential risk to non

- target organisms including
listed and non

- listed terrestrial social invertebrate species. The colony feeding study is designed to represent potential field

- level exposure and account for hive dynamics using longer duration exposure periods than are possible in Tier II tunnel studies. The study will be used to determine whether potential adverse effects to insect pollinators at the whole colony level when bees are able to forage natur ally beyond the spiked food. Results from the feeding study will help to refine the screening

- level risk assessment for beneficial terrestrial invertebrates that were based on Tier I
studies on individual bees. Since feeding studies can help to define a dose

- response relationship at the colony level, the studies can provide a means of determining exposure thresholds below which the likelihood of adverse effects on colonies may be low.

How could the data impact the Agency’s future decision

- making? Tier II colony

- level data will be used to refine screening

- level risk estimates derived using Tier I laboratory

- based data on individual bees. The Tier II data will inform the determination required under FIFRA or the ESA as to whether continued registrat ion of a pesticide is likely to result in
unreasonable adverse effects to non

- target species or is l ikely to adversely affect federally listed
threatened or endangered species or their designated critical habitat. Without these data, EPA may need to presu me risk which will limit the flexibility of pesticide products to comply with FIFRA and
the ESA

, and could result in significant use restrictions.

Study Title: Residues in Pollen and Nectar Rationale for Requiring the Data

Terrestrial invertebrates are likely to be i mpacted if exposed to pesticide residues in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to hive where all life stages may be exposed. For some pesti cides, the quantification of pollinator

- relevant residues in treated flowering plants is needed , since pollinators will be exposed to residues from either current or prior season applications (due to the potential for residues to accumulate in plants and t rees). Residues in edible/transportable

- to

- hive parts of treated trees and plants, including (where appropriate), but not limited to, guttation water, sap/resins, whole plant tissue ( e.g., leaves, stems), as well as blooming, pollen

- shedding, and nectar p roducing parts ( i.e. , flowers and, if present, extra

- floral nectaries) of plants may inform the potential for ris k. Studies should be designed to provide residue data for crops and application methods of concern

.

Page 47 of 48The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance can be found at: http://www2.epa.gov/pollinator

protection/p ollinator

- risk

- assessment

- guidance

.

Practical Utility of the Data

How will the data be used?

Measured residue d ata will be used to refine conservative estimates of pesticide exposure and reduce
uncertainties associated with the Tier I exposure assessment by providing direct measurements of pesticide concentrations resulting from actual use settings. Measured residues may provide a more realistic understanding of exposure through contact or ingestion with which to calculate risk quotients for in dividual bees as well as to characterize exposure to the colony. If measured residue data are not available, risk estimates for terrestrial insects will be based on model

- generated or default values used to support the screening

- level assessment

.

How cou ld the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or
is likely to adversely affect federally listed threatened or endangered species or their designated
critical habitat. Without these data, EPA will have to rely on conservative estimates of exposure
which will limit the flexibility of pesticide products to comply with FIFRA and the ESA

, and could

res ult in use restrictions.

Page 48 of 48