UNITED STA TES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

PC Code: 098701 

DP Barcode: 0424922 

MEMORANDUM Date March 10, 2015 

Subject: 

To: 

From: 

Reviewed: 

Through: 

Registration Review - Preliminary Problem Formulation for Ecological Risk and 

Environmental Fate, Endangered Species, and Drinking Water Assessments for 

Phenmedipham 

Miguel Zavala, Chemical Review Manager 

Neil Anderson, Acting Branch Chief 

Risk Management and Implementation Branch 3 

Pesticide Re-evaluation Division (PRD) 

Amy Blankinship, Chemist ~ }10 \,.r- _ _ ) 

William P. Eckel, Ph.D., Senior Science A ~ /)) J 0 t;) / /J I 

Environmental Risk Branch 6 ./ l/f/~I -lv<-f 5;/c/t( 

Environmental Fate and Effects Division 

Office of Pesticide Programs 

Monica Wait, Risk Assessment Process Leader ~ W ~ ?:>/' b I \ S 

Environmental Risk Branch 6 

Environmental Fate and Effects Division 

Office of Pesticide Programs 

Mark Corbin, Branch Chief f1 I d ILl 

Environmental Risk Branch 6 j1\A.V\J 

Environmental Fate and Effects Division 

Office of Pesticide Programs 

The Environmental Fate and Effects Division (EFED) has completed the preliminary problem 

formulation (attached) for the ecological risk, environmental fate, endangered species, and 

drinking water assessments to be conducted as part of the registration review of the herbicide, 

phenmedipham. The problem formulation draws on information from studies submitted by the 

technical registrants in response to data requirements. This document provides an overview of 

Page I of 48 
what 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 (DCI) to address uncertainties surrounding the environmental 

fate and potential 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 VI

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 48
Table 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 Summary

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 associated with the use of 

phenmedipham as well as uncertainties unique to its risk assessment. This document also 

identifies additional studies that would be beneficial to the conduct of an ecological risk 

assessment. 

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 submitted 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 literature, 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 the 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 validations for parent

phenmedipham and its major degradates in Soil and Water (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 48
one end-use product label (emulsifiable concentrate (EC)) for phenmedipham. 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 this 

document. 

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

MHPC

Chemical Structure of major degradate, MHPC

Page 6 of 48
Laboratory 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.

Toxicity data for desmedipham (PC code 104801), another herbicide with similar chemical 

structure, environmental fate properties, and toxicology as phenmedipham, was used to support 

the risk assessment for the Reregistration Eligibility Decision (RED) when phenmediphamspecific data were not available (USEPA 2005). The chemical structures of desmedipham and 

phenmedipham differ by the placement of one methyl group. 

EFED evaluated the most recent ecological 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. Phenmedipham 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 petition 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) and chemical profile 

reports conducted by BEAD showed usage of phenmedipham on spinach in the top three 

production states (California, New Jersey and Oklahoma), based on available data from 2008—

2012 (USEPA, 2014). The total usage of phenmedipham for spinach 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 used 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 0.975 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 48
Table 1. Profile of currently registered uses of Phenmedipham

Crop

Maximum

Single 

Application

Rate 

(lb a.i./acre)

Annual 

Maximum 

Application 

Rate 

Geographic 

Restrictions

Application 

Method(s)

End-use 

Product 

Labels

Spinach 

(for processing and seed) 0.9751 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 0.4875 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 

assessment 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. Based on the available acute contact data (supported by the desmedipham honey bee 

study), the assessment anticipated that non-target insects will not be at significant acute risk from 

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

MHPC, 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 

requested 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, phenmedipham 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) criteria 

Page 8 of 48
have 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 scenarios. 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. Aerobic 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 supplemental 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 surfaces is very low 

(VP=1E-11mmHg), 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, meta-toluidine,

was observed in hydrolysis and anaerobic metabolism studies. In an aerobic aquatic metabolism

study, which provided limited supplemental data because the sediments were anaerobic, 

phenmedipham degraded with half-lives of 4.7-16.6 days in two water-sediment systems. MHPC 

was the major transformation 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: Physiochemical Properties and Environmental Fate Characteristics of Phenmedipham

Parameter Value1 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 48
Molecular Mass 

of Phenmedipham

(Molecular 

Formula)

Parent: 300.31 

amu

(C16H16N2O4)

MHPC: 167.16 

amu (C8H9NO3)

Herbicide Handbook, Weed Science Society of America 

7th 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 nonionized forms) 

Log octanol-towater partition 

coefficient (KOW) 

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: Halflife

(25±1°C)

50 days pH 5

14.5 hrs pH 7

9.6 min pH 9

40502708 (Acceptable)

Aqueous 

Photolysis: Halflife 

(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, halflife

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 

sedimentstream water)

16.6 days 

(German sand 

sedimentstream water)

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 48
coefficients (Kdads) 

Organic carbonnormalized 

partition

coefficients (KOC)

(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 (Kdads) 

Organic carbonnormalized 

partition 

coefficients (KOC)

(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: Halflife and DT75

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 48
Fish 

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 parent 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 meta-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 the amino-carbonyl linkage yielding methyl 3-

hydroxyphenylcarbamate (MHPC) and m-toluidine, with ultimate formation of carbon

dioxide. Below, Table 3 presents identified major degradates and their maximum percent of 

applied radioactivity.

Table 3. Major Degradates identified and maximum percent of applied radioactivity in 

the fate studies.

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 tables provide a 

preliminary overview of the potential acute toxicity of phenmedipham by providing the acute 

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 48
Acceptable acute toxicity data for freshwater fish and invertebrates were not available for 

phenmedipham (submitted 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 desmedipham were used to bridge phenmedipham 

data gaps, and this approach will be used for registration review. However, in the problem 

formulation 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 freshwater fish (rainbow 

trout LC50 = 1.7 mg a.i./L, MRID 00116714; bluegill sunfish LC50 = 6 mg a.i./L, MRID 

00116713) and freshwater invertebrates (Daphnia magna EC50 = 1.88 mg a.i./L, MRID 

00116712). However, since test concentrations were not measured in the study, these values 

may underestimate the LC/EC50 value. An acute toxicity study with an estuarine/marine mysid 

shrimp (Americamysis bahia) for parent desmedipham resulted in an LC50 value of 1.2 mg a.i./L

(MRID 48587107).

Acute toxicity data for the major phenmedipham degradate, MHPC, were available for 

freshwater fish and invertebrates (MRID 45414203 and 45414202, respectively). The acute LC50

value for rainbow trout and EC50 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 recommended 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 phenmedipham/desmedipham. 

Submitted chronic data for freshwater fish 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, reproduction (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 

EC50, EC20 and EC10 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 EC50 and EC20 and between the EC20 and EC10, thereby introducing 

uncertainty in the reliability of the ECx value. In this study, the phenmedipham 48-hr EC50

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 EC50 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 phenmedipham and MHPC for estimates of acute and chronic toxicity for 

fish and freshwater invertebrates (Appendix B). Predicted fish acute LC50 values ranged from 

2.65-4.92 mg/L for parent phenmedipham. While it is noted that the empirical acute fish LC50

Page 13 of 48
values may be underestimating toxicity, the predicted values are in good agreement with those 

acute fish LC50 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 EC50 value of 1.88 mg/L (Table 4). Estimated chronic toxicity 

values for daphnids were also variable and 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, respectively). 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. 

Parent phenmedipham is short-lived in water at neutral and basic pHs, but longer at acidic pH 

(14.5 hr at pH 7 and 10 minutes at pH 9, yet 50 days at pH 5, MRID 40502708). However, 

MHPC is anticipated to be stable under soil and aquatic conditions. Based on estimated 

environmental concentrations (EECs) calculated in the 2005 RED, the peak EEC for parent 

phenmedipham and MHPC 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/EC50 acute toxicity values may underestimate toxicity due to 

anticipated hydrolysis, based on the peak EEC for phenmedipham, 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 trout) ÷ 17 μg/L (peak EEC) ÷2 = 50). 

Additionally, the acute toxicity LC50 value for the estuarine/marine mysid shrimp was in good 

agreement with the reported EC50 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 LC50 value. Furthermore, the predicted 

acute values for freshwater fish were also in good agreement with the empirical values. 

In regards to chronic toxicity values, for fish, the predicted 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 MHPC since the predicted acute values were greater than the empirical 

values, the predicted chronic values and the empirical acute LC50 value for MHPC are >3,500 

and >17,000 times greater than the peak MHPC EEC. For chronic exposure for Daphnia, using 

the lowest reported ECx value from the open literature study (0.059 mg/L) for phenmedipham, 

this value is 3.5 times greater than the peak EEC. In this study, 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 MHPC were quite 

variable and not always in good agreement with empirical values. However, for daphnids, the 

predicted chronic values and the empirical acute EC50 value for MHPC are >1,600 and >3,000

times greater than the peak MHPC EEC. Estuarine/marine fish acute or chronic or 

estuarine/marine invertebrate toxicity data are not available. However, based on the available 

data, it is not anticipated that estuarine/marine fish or invertebrates would be substantially 

different in their sensitivity to phenmedipham or MHPC. Overall, based on this evaluation, 

additional acute and chronic toxicity data for fish or aquatic invertebrates are not requested for 

parent phenmedipham or MHPC. 

Page 14 of 48
Sediment 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). For 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, chronic sediment studies 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, MHPC, 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), respectively. 

Due to this hydrophilicity, no sediment tests are being requested for MHPC.

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

plant toxicity data (green algae, freshwater and marine diatom, cyanobacteria) toxicity 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 IC50 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 IC50 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 EC50 and EC10 values (based on 

growth rate) for the green algae were ≥0.066 and ≥0.002 mg a.i./L, respectively, and the EC50

was 0.066 mg a.i./L for Lemna minor. In this study, for desmedipham, the green algae EC50

values were ≥0.065 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 ingredient, isophorone (EPA Reg# 264-616). Submitted aquatic animal or plant 

toxicity data for isophorone are not available. However, other information indicates an acute 

LC50 value of 224 mg/L for fish (bluegill sunfish) and acute EC50/LC50 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 chronic 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 48
Table 4. Summary of the Most Sensitive Endpoints from Aquatic Toxicity 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 

fish1

Acute

Rainbow trout 

(Oncorhynchus 

mykiss)

96-Hr LC50 =

1.72

Moderately 

toxic

00237908 (Supplemental3)

Chronic No data

Freshwater 

invertebrates

Acute

Water Flea 

(Daphnia 

magna)

48-Hr EC50 = 

1.882

Moderately 

toxic 0235009 (Supplemental3

)

Chronic

Water Flea 

(Daphnia 

magna)

21-d EC10 = 

0.0594 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)

IC50 >1.02

NOAEC = 1.022

N/A 43053505 (Acceptable)

Tier I study 

Nonvascular

Freshwater

Diatom

Navicula 

pelliculosa

IC50 = 0.14

(0.12-0.17)

NOAEC 

<0.1202,5

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. EC50, EC20 and EC10 values reported in study. It is noted 

that the 95% confidence intervals overlapped between the EC50 and EC20 and between the EC20 and EC10, 

thereby introducing uncertainty in the actual ECx value.

5 Based on the data, an IC05 value was not considered reliable.

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 48
bobwhite quail for desmedipham (LD50 > 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 ≥2,928 

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 (MRID43544902). A statistically 

significant 7.5% reduction in egg shell 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, sublethal effects of reduced body 

weight gain and food consumption were observed in both the mallard and bobwhite subacute 

dietary studies. At the maximum application rate of 0.975 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 subacute 

dietary studies. Therefore, an avian acute oral study using a passerine species is not requested. 

Mammalian toxicity data suggest that phenmedipham (TGAI) is practically non-toxic to small 

mammals on an acute oral basis (rat LD50 >8,000 mg/kg bw; MRID 00067579 & 00076497). In a 

2-generation reproductive toxicity study in rats, the 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/day (44862702 & 45316801).

Acute contact toxicity data to bees for phenmedipham are not available. However, acute toxicity 

data for adult honeybees are available for desmedipham, and the acute oral and contact LD50 values

are >50 μg a.i./bee (MRID 41711402). Chronic toxicity data are not available for adult bees nor 

are acute or chronic data available for larval bees. Data on pollinator toxicity is required to 

sufficiently evaluate risk to pollinators (USEPA 2014a). Therefore, acute 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, MHPC 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 MHPC, 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 MHPC is not requested. 

Page 17 of 48
Terrestrial plant 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 EC25 values 

for the most sensitive monocot and dicot species from both the seedling emergence (the monocot 

wheat EC25 = 1.16 lb a.i./A , the dicot lettuce EC25 = 0.187 lb a.i./A; MRID 46168001) and 

vegetative vigor (the monocot onion EC25 = 0.205 lb a.i./A, and dicot carrot EC25 = 0.169 lb a.i./A; 

MRID 46157701) studies were used to evaluate effects of phenmedipham exposures to non-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

Birds1

Acute

Mallard Duck

(Anas 

platyrhynchos)

21-D 

LD50 > 

2150 mg

a.i./kg-bw2

Practically nontoxic

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 nontoxic

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./kgdiet3

N/A

43544902 (Acceptable)

Endpoints affected: 

eggshell thickness, 

viable embryos, clinical 

signs, male body wt

Mammals Acute Oral

Laboratory rat 

(Rattus 

norvegicus)

LD50

>8000 mg 

a.i./kg-bw 

Practically nontoxic

00067579 & 00076497

(Acceptable)

No mortality.

Page 18 of 48
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

Acute 

Inhalation

No Data (Study 

waived 1/15/88) -- N/A N/A

Chronic Laboratory rat 

2-gen 

NOAEC =

75 mg 

ai/kg/day

LOAEC = 

225 mg 

ai/kg/day

N/A

44862702 & 45316801

(Acceptable)

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 Acute 

contact

Honey bee 

(Apis mellifera L.)

48-Hr 

LD50 > 50

μg a.i./bee 

NOEC = 

36 μg

a.i./bee3

Practically nontoxic

41711402 (Acceptable)

 

Page 19 of 48
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

Acute Oral Honey bee 

(Apis mellifera L.)

48-Hr 

LD50 > 50

μg a.i./bee 

NOEC = 

36 μg

a.i./bee3

NA 41711402 (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 IC25

= 0.187 lbs 

ai/acre

NOAEC = 

0.125 lbs 

ai/acre4

N/A

46168001 (Acceptable)

Monocot – wheat

(Triticum 

aestivum)

21-D IC25

= 1.16 lbs 

ai/acre

NOAEC = 

0.125 lbs 

ae/acre4

N/A

Vegetative 

vigor

Dicot—Carrot 

(Daucus carota)

21-D IC25

= 0.169 lbs 

ai/acre

NOAEC = 

0.125 lbs 

ai/acre4

N/A

46157701 (Acceptable)

Monocot—Onion

(Allium cepa)

21-D IC25

= 0.205 lbs 

ai/acre

NOAEC = 

0.125 lbs 

ae/acre4

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 reported incidents in EIIS 

Page 20 of 48
indicated 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 registrants 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), and ‘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-target 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 (I013246-041and I013246-042), 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 (I013246-041) and 500 of 1000 acres of treated sugar beets

(I013246-042). 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 (normal 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. Flowable concentrate was applied by 

broadcast at a rate of 2 pints/A. Yellowing and stunting were seen in 100% of the treated beet 

crop. Phenmedipham 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 phenmedipham 

are complete and that exposure levels are sufficient to result in field-observable effects to nontarget 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 aquatic and terrestrial organisms. 

The drinking water exposure pathway for birds and mammals was 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. The 

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

Page 21 of 48
potential concern. SIP results are presented in Appendix C. The inhalation exposure pathway 

could not be evaluated using 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). Therefore, the chemical that will be assessed in drinking water from surface and 

ground water is the 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 cropped 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 where in 

question a conservative approach is taken in the selection of half-lives. Descriptions of all 

Page 22 of 48
executable 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 

identified 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 insight 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 Assessment

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 November 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 assessment 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 48
Given that the agencies are continuing to develop and work toward implementation of the 

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

designated critical habitat, 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 registration 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 

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

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of the Problem Formulation for Registration Review for 

phenmedipham, EPA reviewed these data and selected the most sensitive endpoints for relevant 

risk assessment scenarios from the existing hazard database. However, as required by FFDCA 

section 408(p), 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 wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 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 48
of chemicals identified for EDSP screening was published on June 14, 20131 and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. 

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.2

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 environmental 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 48

 
Table 6. Available environmental fate data for phenmedipham and remaining data gaps. 

158

Guideline

(OPPTS)

Description MRID Classification Data 

Gap? Comments

835.4300

(162-4) Aerobic Aquatic 

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 Appendix 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

Supplemental1

No

850.1025

850.1035

850.1045

850.1055 

Saltwater 

invertebrate 

acute toxicity 

48587107 Acceptable1 No

Page 26 of 48
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

850.1075 Freshwater 

fish acute 

toxicity 

00116336/ 

02770201

Invalid No

00116337/ 

02770201

Invalid

00116713 Supplemental1

00116714 Supplemental1

850.1075 Saltwater fish 

acute toxicity 

No data N/A No No studies have been submitted. 

Exposure is estimated to be low.

Parent 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 use 

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 

freshwater 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 unless 

additional data is available. 

Page 27 of 48
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

850.1350 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 unless 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, 

MHPC 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 use 

available freshwater fish toxicity 

data unless additional data is 

available. 

Page 28 of 48
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

850.1500 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 Phenmedipham 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 Phenmedipham 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 Acceptable1 No

850.4500 Algal toxicity 43053504 Acceptable1 No

43053501 Acceptable1

43053503 Acceptable1

44909602 Supplemental

850.4550 Cyanobacteria 43053502 Acceptable No

1 Based on toxicity data for desmedipham

Page 29 of 48
Table 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. 

41607004 Acceptable1

850.2200 Avian dietary 

toxicity 

00115879/ 

27701207

Invalid No

0015850 Invalid

40104501 Supplemental

40104502 Supplemental

850.2300 Avian 

reproduction

44862703 Supplemental No

43544902 Acceptable1

NonguidelineAvian 

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.

NonguidelineHoney bee 

adult acute 

oral toxicity

41711402 Acceptable No

Page 30 of 48
Table 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

NonguidelineHoney 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 development by 

OECD. A protocol should be 

submitted prior to study initiation. 

Study should be conducted with 

phenmedipham acid. 

NonguidelineHoney 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 be 

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 conducted 

using phenmedipham acid. 

NonguidelineHoney bee 

larval chronic 

oral toxicity

No Data N/A Yes

NonguidelineSemi-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 testing 

study may not be needed to complete 

the risk assessment for pollinators. A 

protocol should be submitted prior to 

test initiation

Page 31 of 48
Table 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

NonguidelineField 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 field 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 honey 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 Science 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 Division. June 27, 

2011. DP 384772.

USEPA. 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. Goncalves and F. Goncalves. 2012. Acute and chronic toxicity 

of Betanal® expert and its active ingredients on nontarget aquatic organisms from different 

trophic levels. Environ. Tox. 27(9): 537-548.

USEPA, 2001a. Phenmedipham. Results of the Health Effects Division (HED) Metabolism 

Assessment Review Committee (MARC) Meeting Held on 22-MAY-2001. Chemical#s 128943 

& 129041. Barcode D275136. Case 291904. Submission 8581930. Office of Pesticides Program, 

Health Effects Division, Arlington, VA. June 7, 2001.

Page 33 of 48
Appendix A. Available Toxicity Data for Phenmedipham and 

Desmedipham

Comparison of toxic profiles of Phenmedipham and Desmedipham

Test Desmedipham

Endpoint/Toxicity Classification

Study Classification/ Study MRID

Phenmedipham

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 / 00114111 & 00114112

>5688 & >5790 mg/kg-diet (bobwhite 

quail & mallard duck)/ Practically nontoxic

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 nontoxic

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 48
Acute 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 nonvascular 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/ 46080201

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, PhysProp 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

Carbamate 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 solubility 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 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.

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)

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

MHPC

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

Carbamate 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 111.268

: Daphnid ChV 48.625

: Green Algae ChV 68.083

Note: * = asterisk designates: Chemical may not be soluble enough to

 measure this predicted 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-chronic 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)

Maximum LogKow: 7.0 (Green Algae EC50

Maximum LogKow: 8.0 (ChV)

Page 38 of 48
Maximum 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 EC50 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, Phenyl

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 NOAEC Empirical 

NOAEC

Carbamate 

Esters

Carbamate 

Esters, Phenyl

Phenols Neutral 

Organic

Page 39 of 48
Parent <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 basis.

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 effect 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 is relatively good agreement between the modeled values and the empirical data for fish 

acute toxicity data. Therefore 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

Phenols Neutral 

Organic

Parent 1.7 and 6.0 4.92 2.66 NP 17.7

MHCP 74 143 NP 192 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 25oC; mg/L) 4.7

Mammalian LD50 (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 LD50 (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

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Parameter 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.

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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 exposed. 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. 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 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 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-riskassessment-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-apismellifera-larval-toxicity-test-single-exposure_9789264203723-en .

Practical Utility of the Data

How will the data be used?

The Tier I acute oral toxicity data 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, including 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 of 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 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 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 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 48
brought 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 important 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 Tier 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-no213-honeybees-acute-oral-toxicity-test_9789264070165-en .

Practical Utility of the Data

How will the data be used?

The Tier I chronic oral toxicity data 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. The 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, particularly 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 exposure 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 effects 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 comply 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 exposed. 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 48
provide information on whether 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 laboratory-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 oECD 

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 data 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 

terrestrial 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 potential 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 relative 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 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 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 Testing (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 developing 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 

contaminated 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.

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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 studies under semi-field conditions can be found in the OECD 

Guidance 75 

http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?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 studies 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 

field-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 screening-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 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 may need to presume 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: Pollinator Tier II Semi-Field Toxicity Testing (feeding studies)

Rationale for Requiring the Data

Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently 

brought back to the hive, and may adversely affect developing brood (egg, larvae, 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 means 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 periods 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 effects and/or exposure to pesticide 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 48
forage 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 naturally 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 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 may 

need to presume 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 impacted 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 pesticides, 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 trees). 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 producing parts 

(i.e., flowers and, if present, extra-floral nectaries) of plants may inform the potential for risk. 

Studies should be designed to provide residue data for crops and application methods of concern.

Page 47 of 48
The 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/pollinatorprotection/pollinator-risk-assessment-guidance .

Practical Utility of the Data

How will the data be used?

Measured residue data 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 individual 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 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-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 

result in use restrictions. 

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