UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

MEMORANDUM 

Date: l 7-SEP-2015 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Diqua t Dibromide - Draft Human Health Risk Assessment for Registration 

Review 

PC Code: 03220 I 

Decisio n No.: 482019 

Petition No.: NA 

Risk Assessment Type: Single Chemical/Aggregate 

TXR No.: NA 

MRIO No.: NA 

OP Ba rcode: 04 14 147 

Registra tion No.: NIA 

Regula tory Action: Registration Review Risk Assessment 

Case No.: 0288 

CAS No.: 85-00-7, 2764-72-9 (cation) 

40 CFR: § 180.226 

FROM: Monique M. Perron, Sc.D., Toxicologist 

George F. Kramer, Ph.D., Senior Chemist 

James S. Miller, Environmental Scientist ..,_ ~~.....--.......­

Risk Assessment Branch I (RAB l) 

Health Effects Division (HED; 7509P) 

THROUGH: Thurston G. Morton, Acting Branch Chief 

RAB I !HED (7509P) 

and . 

Jeffrey Dawson A 

Christopher Schlosser 

Risk Assessment Review C'01 

HED (7509P) 

TO: Bonnie Adler 

Pestic ide Re-evaluation Division (PRO; 7508P) 

This document provides the HED's draft human health risk assessment for Registration Review 

of diquat dibromide (6,7-dihydrodipyrido[ 1,2-a:2', 1 '-c]pyrazinediium dibromide). The hazard 

characterization, endpoint selection, and risk assessment were provided by Monique Perron 

(RAB l ); the residue chemistry and dietary exposure assessments were provided by George 

Kramer (RAB I); and the occupational and residential exposure assessment by James Miller 

(RABI). 

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Diquat Dibromide Human Health Risk Assessment 0414147 

Table of Contents 

1.0 Executive Summary ............. ....... ..... ................................................................................. .... 4 

2.0 HED Recommendations ................................. ............................................. ....... .... .............. 6 

2. 1 Data Deficiencies ......................................... .... ................................................ ....... ........... 6 

2.2 Tolerance Considerations ....... .... ..................................... ... .... .... ....... ................................ 7 

2.2. 1 Enforcement Analytical Method ....................................................................................... 7 

2.2.2 Tolerance Recommendations .. ........................................................................................... 7 

2.3 International Harmonization .................................................. ....... .................................. ... 7 

3.0 Introduction .......................................... .... .... ........................... .... .... ....... ... ..................... ... 8 

3. 1 Chemical Identity ........................ ... ..... .... ......... .... .... ............... .............. ........................ .... 8 

3.2 Physical/Chemical Characteristics ..... .... ............. ........ ... ................................ ................... 8 

3 .3 Pesticide Use Pattern .. ........... ............................................................................................ 8 

3.4 Anticipated Exposure Pathways ........................................................ ........... .... ....... ....... ... 9 

3.5 Consideration of Environmental Justice .. ............. ........... ........... ................................... .... 9 

4.0 Hazard Characterization and Dose-Response Assessment.. .............................. ............... 9 

4.1 Toxicology Studies Available for Analysis ....................................................................... 9 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ................................ .... l 0 

4.2.1 Denna! Absorption ............................................................... .................. ......................... 10 

4.3 Summary of Toxicological Effects ... ........ .... ......... .......................................................... 10 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ........................................ 11 

4.4. l Completeness of the Toxicology Database ...................................................................... 11 

4.4.2 Evidence of N'ebrotoxic ity .......................................................... ... .... ............................ .. 11 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ..... ....... .... .. 12 

4.4.4 Residual Uncertainty in the Exposure Database ...... ........................................................ 12 

4.5 Toxicity Endpoint and Point of Departure Selections ..................................................... 12 

4.5.1 Recommendation for Combining Routes of Exposures for Risk Assessment .............. .. 13 

4.5.2 Cancer Classification and Risk Assessment Recommendation ............ ....... ....... ... ......... 13 

4.5.3 Summary of Points of Departure and Toxicity Endpoints Used in Human Health Risk 

Assessment ....................................... ............ ........ .... .................................................................... 14 

4.6 Endocrine Disruptor Screening Program ................................................. ........................ 15 

5.0 Dietary Exposure and Risk Assessment ............................................................ .............. 16 

5.1 Metabolite/Degradate Residue Profile ........................ .... .... ... .... ... .... ....... ... ....... ....... ... ... . 16 

5.1.1 Summary of Plant and Animal Metabolism Studies ....................................................... 16 

5. 1.2 Summary of Environmental Degradation ........................................................................ 17 

5. 1.3 Comparison of Metabolic Pathways ................................................................. .............. . 17 

5. 1.4 Residues of Concern Summary and Rationale ........................ .................. ....... ........... .... 17 

5.2 Food Residue Profile ................................................ ........ ............................................... 17 

5.3 Drinking Water Residue Profile .......... ......... ........ ........ .............. .... .............. ................... 18 

5.4 Dietary (Food + Water) Risk Assessment ............ ....... ........... ..................... .................... 18 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................... ... 18 

6.1 Residential Handler Exposure ........................ ................ ........... .... ... .... ... .... ...... .... ....... ... 18 

6.2 Residential Post-Application Exposure ...................... ..................................................... 20 

6.3 Residential Risk Estimates for Use in Aggregate Assessment.. ...................................... 22 

6.4 Residential Bystander Post-Application Inhalation Exposure ....................................... .. 23 

6.5 Spray Drift ........................................................................ .... ............................... ............ 23 

7.0 Aggregate Exposure/Risk Characterization ......... ............ .... ....... .... ...... ... .... .... ... ... ......... 24 

8.0 Cumulative Exposure/Risk Characterization .................................... .............................. 25 

9.0 Occupational Exposure/Risk Characterization ................................................................ 25 

9.1 Short-/Intermediate-Term Handler Risk ................................................................... .... ... 25 

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9.2 Occupational Post-Application Exposure........................................................................ 31

A.1 Toxicology Data Requirements....................................................................................... 34

A.2 Toxicity Profiles.............................................................................................................. 35

Appendix D. Physical/Chemical Properties................................................................................. 45

Appendix E. Summary of Registered Uses of Diquat ................................................................. 46

Appendix F. International Residue Limits................................................................................... 49

Appendix G. Review of Human Research................................................................................... 53
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1.0 Executive Summary

Background: Diquat dibromide (referred to as diquat for the remainder of this document) is a 

non-selective contact herbicide, algicide, desiccant, and defoliant. It is formulated as a soluble 

concentrate and ready-to-use (RTU) liquid. As an algicide/herbicide, it is used to control aquatic 

and terrestrial weeds through application via direct pouring, hand-held or mechanical sprayer, 

and injection below the water surface. As a terrestrial herbicide and crop desiccant/defoliant, it 

is applied by hand-held sprayer, aircraft, or ground equipment. Its largest use is as a desiccant on 

potatoes. Minor food use applications include use as a desiccant on crops grown for seed. 

Diquat is also used on resistant dormant turf (Bermuda and Zoysia grass) for weed control. 

Additionally, use of irrigation water containing residues of diquat may result in residues in plants 

and livestock.

Dietary exposure is an anticipated exposure pathway as residues of diquat may be found in/on 

crops, livestock commodities, and drinking water. There are residential and aquatic uses of 

diquat and potential for spray drift, so there is exposure in residential and non-occupational 

settings. In an occupational setting, applicators may be exposed while handling the pesticide 

prior to application, as well as during application. There is also potential for post-application 

exposure for workers re-entering treated sites. 

This draft risk assessment (DRA) provides information to support the Registration Review of 

diquat and addresses the exposures and risk estimates associated with all currently registered 

uses. This document incorporates all available data and reflects current HED policies. All data 

requirements identified during the scoping process have been satisfied (B. Daiss; 02-DEC-2009; 

D365773).

Hazard Assessment: The eye was a target organ following subchronic and chronic oral 

exposures in rats, mice, and dogs causing opacity, lesions, discharge, and cataracts. The physical 

properties of diquat indicate it is highly hydrophilic and such chemicals will often cause ocular 

effects due to the high water content of the eye. Clinical signs and body weight decrements were 

noted throughout the database following acute, subchronic, and chronic exposures to diquat. The 

majority of the clinical signs were associated with ocular toxicity (e.g., eye discharge, opaque 

eyes) or general systemic toxicity (e.g., diarrhea, urinary incontinence, lack of grooming). In 

several studies, including the acute neurotoxicity study, there was evidence of potential 

neurotoxicity based on increased incidence of piloerection, abnormal posture and gait, and 

subdued behavior; however, these signs are most likely indicative of overt toxicity rather than 

direct neurotoxicity since they were only seen at the highest dose tested and are consistent with 

those observed at overtly toxic doses in other studies following diquat exposure.

There was no evidence of increased pre- or post-natal susceptibility. The maternal/parental 

effects were consistent with those seen in the toxicological database, and observed at doses at or 

below those producing developmental (decreased fetal body weights and skeletal variations) or 

offspring (reduced number of live pups, kidney lesions, and body weight decrements) effects.

An acceptable route-specific inhalation subchronic toxicity study in rats is available for diquat. 

Portal of entry effects occurred at doses much lower than those eliciting oral toxicity and 

consisted of microscopic lung lesions and increased lung weights in both sexes. 

The diquat risk assessment team recommends that the 10X Food Quality Protection Act (FQPA) 
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Safety Factor (SF) be reduced to 1X for all exposure scenarios for the following reasons: (1) the 

exposure databases are sufficient to determine the nature/magnitude of the residue in food and 

water and exposure analyses are unlikely to underestimate risk of exposure from diquat, (2) there 

is no evidence of increased offspring sensitivity/susceptibility in the database, (3) although there 

is evidence of potential neurotoxicity in the database, the effects are well-characterized with 

clearly established no-observed adverse-effect level (NOAEL)/lowest-observed adverse-effect 

level (LOAEL) values, and selected endpoints are protective for the observed effects.

Dietary Risk Estimates (Food + Drinking Water): Acute and chronic dietary (food and 

drinking water) exposure and risk assessments were conducted using the Dietary Exposure 

Evaluation Model - Food Consumption Intake Database (DEEM-FCID, ver. 3.16) which 

incorporates consumption data from the United States Department of Agriculture (USDA) 

National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA; 2003-2008). For drinking water, the assessments used the Office of 

Water’s Maximum Contaminant Level (MCL; 0.02 ppm), which is considered a worst-case 

estimate. The acute dietary assessment assumed 100% crop treated (CT) and tolerance-level 

residues of diquat for all foods with registered uses. Acute dietary risk estimates were below the

level of concern (LOC) (i.e., <100% of the acute population-adjusted dose; aPAD) for all 

population subgroups. The population subgroup with the greatest exposure and risk estimate was 

children 1-2 years old, which utilized 1% of the aPAD. The chronic assessment was based on 

tolerance-level residues and 100% CT for crops with direct diquat uses (except alfalfa). For 

crops with tolerances to cover irrigation with diquat-treated water, anticipated residue levels 

from irrigation trials were used in conjunction with estimates of percent of crops irrigated. For 

alfalfa, fish, crustaceans, and mollusks, average residues were assumed. Chronic dietary risk 

estimates were below the LOC (i.e., <100% of the chronic population-adjusted dose; cPAD) for 

all population subgroups. The population subgroup with the greatest exposure and risk estimate 

was children 1-2 years old, which utilized 33% of the cPAD.

Residential Risk: There is the potential for residential exposure from the registered uses for 

handlers (i.e., mixing, loading, and applying with manually pressurized handwands and backpack 

sprayers and applying RTU products) and for individuals performing activities on treated turf, in 

treated gardens, and in aquatic areas. For most short-term residential handler and all postapplication exposure scenarios, there are no risk estimates of concern associated with the use of 

diquat (i.e., margins of exposure (MOEs) ≥ 100 for dermal or incidental oral and MOEs ≥ 30 for 

inhalation). However, there are inhalation risk estimates of concern to handlers using backpack 

sprayers to apply to gardens, trees and turf (lawns), and aquatic areas, such as 

recreational/backyard ponds.

Spray Drift: The existing turf post-application assessment is considered protective of spray-drift 

exposure based on the maximum application rate on crops and the existing turf application rates; 

therefore, a separate quantitative spray drift assessment was not conducted. Dermal and 

incidental oral post-application MOEs for turf were not of concern (MOEs ≥ 100).

Aggregate Risk: In accordance with the FQPA, the HED must consider and aggregate (add) 

pesticide exposures and risks from three major sources: food, drinking water, and residential 

exposures. For diquat, acute and chronic aggregate estimates are equivalent to the acute and 

chronic dietary estimates, respectively, and are not of concern. For short- and intermediate-term 

exposures, several scenarios were of concern based on residential handler risk alone; therefore, 

those scenarios cannot be used in aggregate assessment (i.e., these scenarios will also be of 
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concern for aggregate). Using the worst-case residential scenarios that were not of concern, 

short- and intermediate-term aggregate MOEs were not of concern (i.e., MOEs ≥100).

Occupational Risk: There is the potential for occupational exposure from the registered uses of 

diquat. There are no dermal short- or intermediate-term occupational risk estimates of concern 

at baseline (i.e., no gloves) associated with the existing uses of diquat (i.e., MOEs ≥ 100). Some 

occupational scenarios reached acceptable inhalation MOEs at baseline (i.e., no respirator); 

however, several exposure scenarios presented risk estimates of concern (MOE <30) at baseline 

and reached acceptable MOEs with the addition of a respirator or engineering controls. Current 

label personal-protective equipment (PPE) does not require occupational handlers to wear 

respirators. Mixing/loading/applying diquat for mechanically pressurized handguns application 

in greenhouses did not reach acceptable MOEs even with maximum PPE.

An occupational dermal post-application assessment was conducted for workers performing golf 

course maintenance activities on treated turf. There were no risks of concern (i.e., MOEs ≥ 100). 

An occupational post-application risk assessment was not conducted for pre- and post-harvest 

desiccant/defoliant burn-down uses, turf applications to industrial areas, or aquatic uses since

workers are not expected to be in these areas post-treatment or conducting activities that would 

lead to exposure. 

Environmental Justice: Potential areas of environmental justice concerns, to the extent 

possible, were considered in this human health risk assessment, in accordance with U.S. 

Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority 

Populations and Low-Income Populations," 

http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf.

Review of Human Research: This risk assessment relies in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide or other chemical. Please refer to 

Appendix G for a discussion of the human study data used in this risk assessment. 

2.0 HED Recommendations

No additional residue chemistry or toxicological data are required for Registration Review. No 

label changes are required based on residue chemistry. Current tolerances need updated as 

discussed below (Section 2.2.2).

HED calculated inhalation risk estimates that are of concern for residential and occupational 

handlers. For several occupational scenarios, acceptable MOEs were reached with the addition 

of a respirator or engineering controls. Additionally, aquatic use labels need clarification as to 

whether aerial applications are allowed as part of the surface spray application directions for use.

2.1 Data Deficiencies

There are no data deficiencies for the Registration Review of diquat.
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2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

The Pesticide Analytical Manual (PAM) Vol. II. lists a spectrophotometric method, designated 

as Method A (also referenced as Chevron Chemical Company RM-8-7) as available for the 

enforcement of tolerances for residues of diquat per se in/on plant and in livestock commodities. 

In this method, residues are extracted with sulfuric acid to free diquat from the bound state, 

absorbed on cation exchange resin, and eluted with saturated ammonium chloride. The diquat in 

the eluate is reduced with the addition of sodium dithionate, forming an intense green color and 

is measured spectrophotometrically at 337 μm. The limit of quantitation (LOQ) is 0.01 ppm.

The HED has determined that analytical method number RAM 272/02 (“The Determination of 

Residues of Paraquat and Diquat in crops and Soil – A High Performance Liquid 

Chromatographic Method”) is scientifically acceptable as an enforcement method for the 

determination of residues of diquat in crops, including oil seed crops (B. Daiss, 12-MAY-2010; 

D375811). RAM 272/02 has a LOQ in the range of 0.01-0.05 ppm depending on the crop type 

and mass of sample analyzed. With this method, samples are extracted by refluxing in dilute 

sulfuric acid. The filtered digest is diluted and percolated through a column of cation-exchange 

resin that retains diquat. The column is washed with hydrochloric acid, ammonium chloride 

solution to remove endogenous materials. Diquat residues are eluted with saturated ammonium 

chloride solution. A portion of the column eluent is passed through a preconditioned C18 solidphase extraction cartridge to remove further co-extractives. Final determination of diquat 

residues is made using ion-pair high-performance liquid chromatography/ultraviolet 

(HPLC/UV). 

The data requirements for multiresidue methods (MRMs) are fulfilled. The FDA's PESTDATA 

dated 11/6/90 (Pam Vol. I, Appendix) indicates that recovery of diquat using Multiresidue 

Protocols is unlikely. The updated PESTDATA dated 08/93 does not have an entry for diquat.

2.2.2 Tolerance Recommendations

Permanent tolerances have been established in 40 CFR §180.226 for residues of the plant growth 

regulator and herbicide diquat, (6,7-dihydrodipyrido (1,2-a:2′1′-c)pyrazinediium) derived from 

application of the dibromide salt and calculated as the cation in/on various raw agricultural 

commodities, ranging from 0.02 ppm to 20.0 ppm.

Appendix C is a summary of the established and HED-recommended tolerances for residues of 

diquat per se. 

2.3 International Harmonization

The U.S. residue definitions are harmonized with Canada and Codex. The U.S. tolerances and 

Canadian and Codex maximum residue limits (MRLs) are harmonized for several commodities 

(bulb vegetables, potato, pome fruit, and stone fruit). For several commodities, the U.S. 

tolerances are harmonized with either the Canadian or the Codex MRL (livestock commodities, 

berry and small fruit group, cereal grain group, tree nuts, cucurbit vegetables, root and tuber 

vegetables, and beans (dry)). For bananas and coffee, HED is recommending that the U.S. 

tolerances (0.05 ppm) be harmonized with the Codex MRLs (0.02 ppm) as there are no U.S. 
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registrations for these crops. For the following crops, the U.S. tolerance values are either 

significantly higher or lower than the Canadian and/or the Codex MRLs, precluding 

harmonization: canola, milk, citrus fruit, Brassica leafy vegetables, foliage of legume 

vegetables, fruiting vegetables, oilseeds, and legume vegetables (except dry beans). For a 

summary of U.S. tolerances and international MRLs, refer to Appendix F.

2.4 Label Recommendations

A summary of risk estimates has been provided, and shows that there are residential and 

occupational risk estimates of concern for registered uses of diquat based on the use information, 

label-required PPE, and restricted-entry intervals (REIs).

Additionally, aquatic use labels need clarification as to whether aerial applications are allowed as 

part of the surface spray application directions for use (see Section 6.5).

3.0 Introduction

3.1 Chemical Identity

The chemical structure and nomenclature of diquat is presented in Table 3.1.1. 

Table 3.1.1. Nomenclature for Diquat.

Chemical Structure

Common name Diquat dibromide

Company experimental name NA

IUPAC name 9,10-dihydro-8a,10a-diazoniaphenanthrene dibromide

CAS name 6,7-dihydrodipyrido[1,2-a:2′,1′-c]pyrazinediium dibromide

CAS # 85-00-7, 2764-72-9 (cation)

3.2 Physical/Chemical Characteristics

Pure diquat dibromide is an odorless, colorless to yellow crystal. It is hydrophilic with a log 

octanol-water partition coefficient (Kow) of -4.60 and very soluble in water, slightly soluble in 

alcohol and hydroxylic solvents, and insoluble in non-polar organic solvents. It is susceptible to 

ultraviolet decomposition. It has a low vapor pressure of <1×10

-8 mm Hg at 25°C. A detailed 

description of the physicochemical properties of diquat is provided in Appendix D. 

3.3 Pesticide Use Pattern

Diquat is used as an herbicide/algaecide, and is formulated as a soluble concentrate (SC) and a 

RTU intended for use on aquatic, terrestrial, and non-terrestrial weeds, and as a pre-harvest 

desiccant and post-harvest defoliant on various crops. Tolerances derived from application of

diquat in/on food commodities include alfalfa, bananas, canola, coffee, clover, potatoes, and 

livestock commodities. Based on aquatic application of diquat and use of irrigation water 
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containing residues of diquat, tolerances have been established for residues in/on additional 

commodities/crop groups (see Appendix C).

Diquat is applied by direct pouring, handheld or mechanical sprayer, injection below the water 

surface, aircraft, and ground equipment. Maximum application rates vary according to use 

description. Maximum application rates for occupational use sites range from 0.25 lb/A to 0.5 lb 

ai/acre for terrestrial, non-crop terrestrial, and farmland uses, and 4 lb ai/acre/4 ft to 0.04 lb ai/gal 

for applications to aquatic areas such as lakes and ponds. Maximum application rates for 

residential use sites range from 0.5 lb ai/acre to 0.01 lb ai/gal for gardens, trees, and turf 

(resistant dormant Bermuda and Zoysia) and up to 0.000092 lb ai/ft2for aquatic uses such as 

backyard ponds. Appendix E provides a summary of the registered uses of diquat.

3.4 Anticipated Exposure Pathways

Based on the registered diquat application scenarios, dietary exposure is an anticipated exposure 

pathway as residues of diquat may be found in/on crops, livestock commodities, and drinking 

water. There are residential and aquatic uses of diquat and potential for spray drift, so there is 

exposure in residential and non-occupational settings. In an occupational setting, applicators 

may be exposed while handling the pesticide prior to application, as well as during application. 

There is also potential for post-application exposure for workers re-entering treated sites. This 

risk assessment considers all of the aforementioned exposure pathways based on the existing 

uses of diquat.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf). As a part of every 

pesticide risk assessment, the Office of Pesticide Programs (OPP) considers a large variety of 

consumer subgroups according to well-established procedures. In line with OPP policy, HED 

estimates risks to population subgroups from pesticide exposures that are based on patterns of 

that subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA’s NHANES/WWEIA and are used in pesticide risk assessments for all registered 

food uses of a pesticide. These data are analyzed and categorized by subgroups based on age and 

ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, specialized 

subgroups and exposure assessments are performed when conditions or circumstances warrant. 

Whenever appropriate, non-dietary exposures based on home use of pesticide products and 

associated risks for adult applicators and for toddlers, youths, and adults entering or playing on 

treated areas post-application are evaluated. Further considerations are currently in development 

as OPP has committed resources and expertise to the development of specialized software and 

models that consider lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicological database for diquat is complete and adequate for hazard characterization, 

toxicity endpoint selection, and FQPA SF evaluation. Since the last risk assessment (B. Daiss; 
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12-MAY-2010; D372014), an acceptable immunotoxicity study has been submitted and 

reviewed.

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

Diquat was poorly absorbed from the intestinal tract when administered orally as 14C-diquat 

dibromide with approximately 90% of the radioactivity eliminated via the feces following oral 

dosing. After a subcutaneous injection to circumvent the intestine, nearly all of the labeled 

material was recovered in the urine after 2 days. This is consistent with the physical/chemical 

properties of diquat indicating it is a highly hydrophilic compound (log Kow = -4.6). Diquat did 

not significantly accumulate in tissues by either route of administration. Some retention was 

noted in the kidney after repeated oral dosing. Intravenous injection results indicated diquat 

concentrated in cartilaginous tissues, liver, and urinary bladder, as well as the brain and spinal 

cord. 

Rats excreted 6.3% and 89.3% of the radioactivity in the urine and feces, respectively, within 4 

days following oral exposure, with most being excreted within the first 48 hours. In the urine, 

most of the excreted radioactivity (5.3%) was the unchanged parent compound, whereas the 

remaining 1% was associated with diquat monopyridone (0.2%), diquat dipyridone (0.1%), and 

unidentified metabolites (0.3%). In the feces, 65.5% of excreted radioactivity was detected in 

the sulfuric acid-extractable fraction and 15.7% in the ammonium sulfate-unextractable fraction. 

In the sulfuric acid fraction, the radioactivity was distributed as unchanged diquat (57.1%), 

diquat monopyridone (4.3%), and unidentified material (4.1%). The ammonium sulfate fraction 

was not analyzed for metabolites. Following subcutaneous injection, most the radioactivity 

(87.1%) was excreted as unchanged parent in the urine after 4 days.

4.2.1 Dermal Absorption

In a rat dermal-penetration study (MRID 41238701), absorption of diquat was found to be 

relatively low following application of 0.05, 0.5, and 5 mg diquat cation/rat to a 10-cm2area for 

2-, 10-, and 24-hour exposures. After 10 hours of exposure, absorption (sum of dose measured 

on/in skin, blood, urine, feces, carcass, and cage wash) was 5.5%, 5.5%, and 2.5% at 0.05, 0.5, 

and 5 mg/rat, respectively. 

A human dermal absorption study from the literature (MRID 43736616)1 was cited by the 

registrant in comments to the Tolerance Reassessment Eligibility Document (TRED) (B. Daiss; 

25-MAR-2002; D281890). The study has been subjected to ethics review and was used to 

update dermal exposure values originally reported in the TRED (B. Daiss; 13-MAR-2002; 

D28163). Using the data from this human study, a dermal absorption factor (DAF) of 0.3% will 

be applied to convert oral doses to dermal equivalent doses since an oral toxicity study was 

selected to assess risks from dermal exposures (see Section 4.5).

4.3 Summary of Toxicological Effects

The eye was a target organ following subchronic and chronic oral exposures in rats, mice, and 

dogs causing opacity, lesions, discharge, and cataracts. The physical properties of diquat 

indicate it is highly hydrophilic and such chemicals will often cause ocular effects due to the 

 

1 Feldman, RJ and Maibach, HI. 1974. Percutaneous penetration of some pesticides and herbicides in man. Tox. 

Appl. Pharm. 28: 126-132.
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high water content of the eye. Clinical signs and body weight decrements were noted throughout 

the database following acute, subchronic, and chronic exposures to diquat. The majority of the 

clinical signs in rats, mice, and dogs were associated with ocular toxicity (e.g., eye discharge, 

opaque eyes) or general systemic toxicity (e.g., diarrhea, urinary incontinence, lack of 

grooming). Clinical signs associated with general systemic toxicity were also seen in rabbits; 

however, there were no ocular effects observed in this species. In several studies, including the 

acute neurotoxicity study, there was evidence of potential neurotoxicity based on increased 

incidence of piloerection, abnormal posture and gait, and subdued behavior; however, these signs 

are most likely indicative of overt toxicity rather than direct neurotoxicity since they were only 

seen at the highest dose tested and are consistent with those observed at overtly toxic doses in 

other studies following diquat exposure. 

There was no evidence of increased pre- or post-natal susceptibility. The maternal/parental 

effects were consistent with those seen in the toxicological database, and observed at doses at or 

below those producing developmental (decreased fetal body weights and skeletal variations) or 

offspring (reduced number of live pups, kidney lesions, and body weight decrements) effects.

An acceptable route-specific inhalation subchronic toxicity study in rats is available for diquat. 

Portal of entry effects occurred at doses much lower than those eliciting oral toxicity and 

consisted of microscopic lung lesions and increased lung weights in both sexes. 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

The diquat risk assessment team recommends that the 10X FQPA SF be reduced to 1X for all 

exposure scenarios. The exposure databases are sufficient to determine the nature/magnitude of 

the residue in food, and dietary exposure analyses are unlikely to underestimate risk of exposure 

from diquat. Additionally, there is no evidence of increased offspring sensitivity/susceptibility in 

the database. Although there is evidence of potential neurotoxicity in the database, the effects 

are well-characterized with clearly established NOAEL/LOAEL values, and selected endpoints 

are protective for the observed effects.

4.4.1 Completeness of the Toxicology Database

The existing toxicological database is complete and adequate for characterizing diquat toxicity 

and quantifying hazard for dietary, residential, and occupational exposures. The developmental 

toxicity studies in rats, rabbits, and mice, as well as the two-generation reproduction toxicity 

study in rats, are available to assess potential fetal/offspring sensitivity. The acute and chronic 

neurotoxicity studies are available to assess potential neurotoxicity.

4.4.2 Evidence of Neurotoxicity

Although there was evidence of potential neurotoxicity (increased incidence of piloerection, 

abnormal posture and gait, and subdued behavior) in several studies in the diquat database, 

concern is low since 1) the effects are well-characterized with clear NOAEL/LOAEL values, 2) 

there was no additional evidence of potential neurotoxicity in the rest of the database, including 

the subchronic neurotoxicity study, and 3) selected endpoints are protective of the observed 

effects.
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4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There was no evidence of increased offspring sensitivity/susceptibility following diquat 

exposure.

4.4.4 Residual Uncertainty in the Exposure Database

The exposure databases are sufficient to determine the nature/magnitude of the residue in food

and drinking water. The dietary exposure analyses are unlikely to underestimate exposure as 

they incorporated tolerance-level residues, 100% CT, and MCL-level residues in water. The 

residential post-application exposure assessments are based upon the 2012 Residential Standard 

Operating Procedures (SOPs). These assessments of exposure are not likely to underestimate the 

resulting estimates of risk from exposure to diquat.

4.5 Toxicity Endpoint and Point of Departure Selections

Since the last risk assessment for diquat, the classification of the mouse developmental study has 

been changed to unacceptable due to poor dosing/intubation errors. Additionally, 

NOAEL/LOAEL values and statements have been updated for the developmental rat, 

developmental rabbit, and chronic dog studies to reflect current policies. The changes in these 

decisions did not impact the studies selected for endpoint selection; however, the value for the 

point of departure (POD) was revised for incidental oral and dermal exposures to reflect the 

updated NOAEL/LOAEL values in the developmental rabbit study. Additional studies in the 

database were not updated to reflect current policies since these changes would not affect current 

PODs and the selected endpoints are protective of all effects seen in the diquat database.

Acute Dietary (all populations): The acute reference dose (aRfD) for all populations was 

established using the NOAEL of 75 mg/kg/day from the acute neurotoxicity study. The LOAEL 

of 150 mg/kg/day is based on increased incidence of clinical signs, such as piloerection, diarrhea, 

urinary incontinence, upward curvature of the spine, and subdued behavior. Similar clinical 

signs were seen in the developmental studies in rats and rabbits at lower doses, but only after 

repeated dosing. This study is appropriate for the duration and route of exposure. There were no 

other effects in the database considered to be attributable to a single dose. The aPAD of 0.75 

mg/kg/day is derived from the NOAEL of 75 mg/kg/day and a 100-fold uncertainty factor (UF) 

(10X for interspecies extrapolation, 10X for intraspecies variation, and 1X for FQPA SF).

Chronic Dietary (all populations): The chronic reference dose (cRfD) for all populations was 

established using the NOAEL of 0.5 mg/kg/day from the chronic oral toxicity study in dogs. The 

LOAEL of 2.5 mg/kg/day is based on cataracts in females. Similar NOAEL/LOAEL values 

were obtained in the rat reproduction toxicity and rat chronic/carcinogenicity studies. The 

chronic oral toxicity study in dogs is appropriate for the duration and route of exposure. The 

study is protective of effects seen following chronic exposure in all species. The cPAD of 0.005 

mg/kg/day is derived from the NOAEL of 0.5 mg/kg/day and a 100-fold UF (10X for 

interspecies extrapolation, 10X for intraspecies variation, and 1X for FQPA SF). 

Short- and Intermediate-Term Incidental Oral: The developmental toxicity study in rabbits was 

selected to evaluate incidental oral exposures (maternal NOAEL = 3 mg/kg/day). The maternal 

LOAEL of 10 mg/kg/day is based on an increased incidence of clinical signs (diarrhea, subdued 

appearance, and thin appearance). The endpoint is appropriate for the duration and route of 
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exposure. Although the effects were seen in adult animals, similar NOAEL/LOAEL values were 

seen for offspring in the reproduction toxicity study; therefore, it is still considered appropriate 

for the population of concern. The LOC for incidental oral exposures is for MOEs less than 100 

(10X for interspecies extrapolation, 10X for intraspecies variation, and 1X for FQPA SF).

Short- and Intermediate-Term Dermal: The developmental toxicity study in rabbits was selected 

to evaluate incidental oral exposures (maternal NOAEL = 3 mg/kg/day). The maternal LOAEL 

of 10 mg/kg/day is based on an increased incidence of clinical signs (diarrhea, subdued 

appearance, and thin appearance). The endpoint is appropriate for the duration of exposure. 

Although subchronic dermal toxicity studies are available for diquat in the rat and rabbit, these 

studies were not selected due to concerns that the skin was compromised. As a result, an oral 

study was selected to evaluate dermal exposure. The LOC for dermal exposures is for MOEs 

less than 100 (10X for interspecies extrapolation, 10X for intraspecies variation, and 1X for 

FQPA SF when applicable). Since an oral study was selected, a DAF of 0.3% should be applied 

for all dermal exposure scenarios.

Short- and Intermediate-Term Inhalation: The route-specific subchronic inhalation study in rats 

was selected to evaluate inhalation exposures with a NOAEL of 0.1 μg/L. The LOAEL of 0.49 

μg/L is based on increased mean lung weights and microscopic lesions. Human-equivalent

concentrations (HECs) for residential and occupational scenarios were derived using the NOAEL 

and the regional deposited-dose ratio (RDDR). The RDDR accounts for the particulate diameter 

[mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD)] and 

estimates the different dose fractions deposited along the respiratory tract. The RDDR also 

accounts for interspecies differences in ventilation and respiratory tract surface areas. For the 

subchronic inhalation toxicity study with diquat, a RDDR was estimated at 0.591 based on the 

pulmonary effects seen at the LOAEL of 0.49 μg/L, with a MMAD of 1.9 μm and GSD of 1.9. 

Human-equivalent doses were subsequently calculated from the HECs for residential and 

occupational handler scenarios. For occupational handlers, human-equivalent doses of 0.0025, 

0.0051, and 0.0088 mg/kg/day correspond to breathing rates of 8.3 L/min, 16.7 L/min, and 29 

L/min. For residential handlers and swimmers, the human-equivalent dose of 0.0017 mg/kg/day 

is only calculated for the 16.7 L/min breathing rate. HEC and human-equivalent dose

calculations are summarized in Appendix B. The standard interspecies extrapolation UF can be 

reduced from 10X to 3X due to the calculation of HECs accounting for pharmacokinetic (not 

pharmacodynamic) interspecies differences. Therefore, the LOC for inhalation exposures is for 

MOEs less than 30 (3X for interspecies extrapolation, 10X for intraspecies variation, and 1X for 

FQPA SF when applicable). 

4.5.1 Recommendation for Combining Routes of Exposures for Risk Assessment

Based upon common effects and the use the rabbit developmental toxicity study for incidental 

oral and dermal routes, these exposures can be combined. Common effects were not seen in the 

route-specific inhalation study in rats; therefore, inhalation exposures may not be combined with 

these routes.

4.5.2 Cancer Classification and Risk Assessment Recommendation

Diquat is classified as a Category E (evidence of non-carcinogenicity to humans) chemical based 

on no evidence of carcinogenicity in rats and mice. The weight of evidence was predominantly 
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negative for mutagenicity.

4.5.3 Summary of Points of Departure and Toxicity Endpoints Used in Human Health 

Risk Assessment

Table 4.5.3.1. Summary of Toxicological Doses and Endpoints for Diquat for Use in Dietary and NonOccupational Human Health Risk Assessments.

Exposure/ 

Scenario POD Uncertainty/FQPA SF

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(All 

populations)

NOAEL = 

75 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

aRfD =

0.75 mg/kg/day

aPAD = 

0.75 mg/kg/day

Acute Neurotoxicity Study in Rats

LOAEL = 150 mg/kg/day based on 

clinical signs.

Chronic 

Dietary (All 

Populations)

NOAEL = 

0.5 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

cRfD =

0.005 mg/kg/day

cPAD = 

0.005 mg/kg/day

Chronic Toxicity in Dogs

LOAEL = 2.5 mg/kg/day based on 

cataracts in females.

Incidental Oral 

Short-Term 

(1-30 days) and 

IntermediateTerm 

(1-6 months)

NOAEL = 

3 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential LOC 

for MOE = 100

Developmental Toxicity Study in 

Rabbits

LOAEL = 10 mg/kg/day based on 

clinical signs.

Dermal ShortTerm 

(1-30 days) and 

IntermediateTerm 

(1-6 months)

NOAEL = 

3 mg/kg/day

DAF = 0.3%

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential LOC 

for MOE = 100

Developmental Toxicity Study in 

Rabbits

LOAEL = 10 mg/kg/day based on 

clinical signs.

Inhalation 

Short-Term 

(1-30 days) and 

Intermediateterm 

(1-6 months)

NOAEL = 

0.1 μg/L

UFA = 3X

UFH = 10X

FQPA SF = 1X

Residential LOC 

for MOE = 30

Subchronic Inhalation Toxicity 

Study in Rats

LOAEL = 0.49 μg/L based on 

increased mean lung weights and 

microscopic lesions in the lung.

Cancer (oral, 

dermal, 

inhalation)

Classified as “Category E – evidence of non-carcinogenicity to humans.”

Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark 

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = 

no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. UFA = extrapolation 

from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). FQPA SF = FQPA Safety Factor. PAD = population-adjusted dose (a = acute, c = chronic). RfD = reference 

dose. MOE = margin of exposure. LOC = level of concern. 
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Table 4.5.3.2. Summary of Toxicological Doses and Endpoints for Diquat for Use in Occupational Human 

Health Risk Assessments.

Exposure/ 

Scenario POD UFs LOC for Risk Assessment Study and Toxicological Effects

Dermal

Short-Term 

(1-30 days) 

and 

IntermediateTerm 

(1-6 months)

NOAEL = 

3 mg/kg/day

DAF = 0.3%

UFA = 10X

UFH = 10X

FQPA SF = 1X

Occupational LOC 

for MOE = 100

Developmental Toxicity Study in 

Rabbits

LOAEL = 10 mg/kg/day based on 

clinical signs.

Inhalation 

Short-Term 

(1-30 days) 

and 

Intermediateterm 

(1-6 months)

NOAEL = 

0.1 μg/L

UFA = 3X

UFH = 10X

FQPA SF = 1X

Occupational LOC 

for MOE = 30

Subchronic Inhalation Toxicity 

Study in Rats

LOAEL = 0.49 μg/L based on 

increased mean lung weights and 

microscopic lesions in the lung.

Cancer (oral, 

dermal, 

inhalation)

Classified as “Category E – evidence of non-carcinogenicity to humans.”

Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark 

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = 

no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. UFA = extrapolation 

from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). MOE = margin of exposure. LOC = level of concern. 

4.6 Endocrine Disruptor Screening Program

As required by Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Federal Food, 

Drug, and Cosmetic Act (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 that may be 

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

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

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

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

taxonomic groups. As part of its reregistration decision for diquat, 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), diquat 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.
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Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between

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

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

of chemicals identified for EDSP screening was published on June 14, 20132and 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.3

5.0 Dietary Exposure and Risk Assessment 

G. Kramer, 17-SEP-2015, D417172

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

The qualitative nature of the residue in plants (primary and rotational) is adequately understood 

based on an acceptable potato metabolism study and a rat bioavailability study. The HED 

Metabolism Assessment Review Committee (MARC) has concluded that the terminal residue of 

concern in plants is the diquat cation (T. Morton, 08-NOV-2001; D277765). The established 

tolerance expression for residues of diquat in/on plant (primary and rotational) commodities is 

appropriate and no changes are required.

The potato metabolism study indicated that no metabolism of diquat occurred in potato tubers 

following preharvest application of [14C]-diquat as a desiccant to potato stalks and stems. 

Previously submitted soybean and wheat metabolism studies were deemed marginal because of 

inadequate characterization and identification of 14C-residues in the commodities of concern. In 

lieu of additional crop metabolism studies, HED recommended several alternatives for this 

requirement. The registrant opted to conduct a bioavailability study. The results of the 

bioavailability study showed that diquat plant residues are largely not bioavailable; <5% of the 

14C is absorbed as a result of feeding diquat field residues in/on wheat chaff to rats. In addition, 

there was minimal uptake of residues in the confined rotational crop study.

The qualitative nature of the residue in livestock and fish/shellfish is adequately understood 

based on acceptable poultry, ruminant, and fish metabolism studies. The metabolism studies on 

ruminants, fish, and poultry showed that parent compound is the only significant residue in 

muscle, fat, and milk. In liver, kidney, and eggs, however, the presence of the predominant 

metabolites 1-oxo-1,2,3,4-tetrahydropyrido[1,2-a]pyrazin-5-ium (TOPPS), diquat monopyridone, 

and diquat dipyridone indicated extensive degradation of the parent compound. The HED 

MARC has concluded the residue of concern for livestock and fish/shellfish is the diquat cation 

(T. Morton, 08-NOV-2001; D277765). The established tolerance expression for residues of 

diquat in livestock commodities is appropriate and no changes are required.

 

2

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

3 See http://www.epa.gov/endo/.
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5.1.2 Summary of Environmental Degradation

Diquat is persistent but essentially immobile in the environment, indicating that it will most likely 

be associated with the soil and sediment instead of water. The primary route of environmental 

dissipation of diquat used in terrestrial settings is strong adsorption to soil. When used as an 

aquatic herbicide, diquat is removed from the water column by adsorption to sediment, aquatic 

vegetation, and organic matter. Based on acceptable guideline studies, diquat does not hydrolyze or 

photodegrade, and is resistant to microbial degradation under aerobic and anaerobic conditions. 

There were no major degradates isolated from any of the environmental fate studies. 

Environmental fate data indicate that diquat is miscible in water (7 x 105ppm), is stable to 

hydrolysis, photolysis, and metabolism, but is essentially immobile in soil and sediment. The 

extent of adsorption appears to be related to soil pH, with is consistent with cation exchange in soil.

5.1.3 Comparison of Metabolic Pathways

The general metabolic pathways in rodents and livestock were found to be comparable, involving 

successive oxidations followed by cleavage of the parent molecule. No metabolites were 

identified in the plant and fish metabolism studies.

5.1.4 Residues of Concern Summary and Rationale

The residues of concern in primary crops, rotational crops, livestock, and drinking water, as 

identified by the MARC, are shown in Table 5.1.4 below.

Table 5.1.4. Residues of Concern in Crops, Livestock, and Drinking Water.

Matrix Residues of Concern for Tolerance Expression Residues of Concern for Risk Assessment

Primary Crops Diquat Diquat

Rotational Crops Diquat Diquat

Livestock and fish/shellfish Diquat Diquat

Water Not applicable Diquat

5.2 Food Residue Profile

Tolerances are currently established under 40 CFR §180.226(a)(1) for residues of the plant growth 

regulator and herbicide diquat, derived from application of the dibromide salt and calculated as the 

cation, resulting from direct uses of diquat. Tolerance levels range from 0.02 to 6.0 ppm. In 

addition, permanent tolerances are established under 40 CFR §180.226(a)(1) for residues of the 

herbicide diquat (calculated as the cation) derived from the aquatic application of the dibromide 

salt in/on numerous food commodities; these established tolerances range from 0.02 ppm (various 

plant commodities) to 20 ppm (shellfish). Tolerances of diquat have also been established under 

40 CFR §180.226(a)(3) and 40 CFR §180.226(a)(4) for imported coffee and bananas and the 

processed commodities of soybean and potato, respectively.

The submitted field trial residue data for all registered crops are adequate. The field trial data 

reflect the registered use patterns; an adequate number of trials were conducted in the appropriate 

geographic regions; and samples were analyzed for the residue of concern using validated datacollection methods. The storage intervals were also validated. The data requirements for 

magnitude of the residue in livestock and fish/shellfish are also fulfilled. There are no outstanding 

residue chemistry data gaps. HED is recommending that tolerances be established under 40 CFR 

§180.226(a)(1) for residues of diquat derived from the aquatic application of the dibromide salt 
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in/on crop groups 2, 3, 18, 19, and 20 in order to support irrigation of all food/feed crops.

5.3 Drinking Water Residue Profile

As per the 2002 Tier 1 drinking water assessment4, the Office of Water’s MCL (0.02 ppm), 

which is considered a worst-case estimate, was assumed for both the acute and chronic 

assessments. 

5.4 Dietary (Food + Water) Risk Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using DEEM-FCID (ver. 3.16) which incorporates consumption data from the 

USDA NHANES/WWEIA; 2003-2008. For drinking water, the assessments used the MCL of 

0.02 ppm, which is considered a worst-case estimate. The acute dietary assessment assumed

100% CT and tolerance-level residues of diquat for all foods with registered uses. Acute dietary 

risk estimates were below the LOC (i.e., <100% of the aPAD) for all population subgroups. The 

population subgroup with the greatest exposure and risk estimate was children 1-2 years old, 

which utilized 1% of the aPAD. The chronic assessment was based on tolerance-level residues 

and 100% CT for crops with direct diquat uses (except alfalfa). For crops with tolerances to 

cover irrigation with diquat-treated water, anticipated residue levels from irrigation trials were 

used in conjunction with estimates of percent of crops irrigated. For alfalfa, fish, crustaceans, 

and mollusks, average residues were assumed. Chronic dietary risk estimates were below the 

LOC (i.e., <100% of the cPAD) for all population subgroups. The population subgroup with the 

greatest exposure and risk estimate was children 1-2 years old, which utilized 33% of the cPAD.

Table 5.4.1. Summary of Dietary (Food + Drinking Water) Exposure and Risk for Diquat.

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

General U.S. Population 0.007855 1 0.000808 16

All Infants (<1 year old) 0.005755 1 0.001518 30

Children 1-2 years old 0.009535 1 0.001673 33

Children 3-5 years old 0.008057 1 0.001387 28

Children 6-12 years old 0.006941 1 0.000942 19

Youth 13-19 years old 0.004296 1 0.000626 12

Adults 20-49 years old 0.008672 1 0.000745 15

Adults 50-99 years old 0.008203 1 0.000723 14

Females 13-49 years old 0.006255 1 0.000702 14

The highest exposure/risk estimate for each duration is bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

J. Miller, 17-SEP-2015, D427297

6.1 Residential Handler Exposure

The HED uses the term “handlers” to describe those individuals who are involved in the 

pesticide application process. The HED believes that there are distinct tasks related to 

 

4 Tier I Drinking Water and Aquatic Ecological Exposure Assessments for Diquat Dibromide. J Breithaupt (05-

MAR-2002, D281199)
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applications and that exposures can vary depending on the specifics of each task. Residential 

handlers are addressed somewhat differently by the HED as homeowners are assumed to 

complete all elements of an application (mixing, loading, and application) without use of any 

protective equipment.

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, short-term residential handler dermal and inhalation exposures are 

expected from the existing uses of diquat. The quantitative exposure/risk assessment developed 

for residential handlers is based on the following scenarios: 

 Mixing/loading/applying with manually pressurized handwand: gardens/trees/turf 

(around the home and garden), residential lawns, ornamentals, and greenhouses. Aquatic 

herbicide/algaecide uses include recreational/backyard ponds. 

 Mixing/loading/applying with backpack sprayer: gardens/trees/turf (around the home 

and garden). Aquatic herbicide/algaecide uses include recreational/backyard ponds. 

 Applying with RTU trigger-spray bottle: gardens/trees/turf (around the home and 

garden).

A series of assumptions and exposure factors served as the basis for completing the residential 

handler risk assessments. Assumptions and factors, as well as algorithms used to estimate noncancer exposure and dose for residential handlers, are detailed in the most recent occupational 

and residential exposure (ORE) assessment memo (J. Miller; 17-SEP-2015; D427297). 

Table 6.1.1 is a summary of residential handler risk estimates. For most short-term residential 

handler scenarios, there are no risk estimates of concern associated with the use of diquat (i.e., 

MOEs ≥ 100 for dermal and MOEs ≥ 30 for inhalation); however, the following inhalation 

exposure scenarios presented risk estimates of concern for residential handlers:

 Backpack sprayer applications to gardens, trees and turf (lawns) 

 Aquatic uses for recreational/backyard ponds.

Table 6.1.1. Residential Handler Non-Cancer Exposure and Risk Estimates for Diquat.

Exposure 

Scenario

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Max. 

App.

Rate1

Area Treated 

or Amount 

Handled 

Daily2

Dermal Inhalation

Dose 

(mg/kg/day)3

MOE4

(LOC = 100)

Dose 

(mg/kg/day)5

MOE6

(LOC = 30)

Mixer/Loader/Applicator (Soluble Concentrate)

Manually 

Pressurized 

Handwand/

Handgun to 

Turf/Gardens 

/Trees

63 0.018 0.01

lb ai/gal

5 gal

0.00012 25,000 0.00001 150

Backpack Sprayer 

to Turf

130 0.14 0.01

lb ai/gal 0.00024 12,000 0.00008 20 Backpack Sprayer 

to Gardens and 

Trees

Trigger-Spray 

Bottle

to Gardens and 

85.1 0.061

0.0025

lb ai/

bottle7

2 bottles 0.000016 190,000 0.0000038 450
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Table 6.1.1. Residential Handler Non-Cancer Exposure and Risk Estimates for Diquat.

Exposure 

Scenario

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Max. 

App.

Rate1

Area Treated 

or Amount 

Handled 

Daily2

Dermal Inhalation

Dose 

(mg/kg/day)3

MOE4

(LOC = 100)

Dose 

(mg/kg/day)5

MOE6

(LOC = 30)

Trees

Trigger-Spray 

Bottle

to Gardens and

Trees

1 bottle 0.000008 380,000 0.0000019 890

Aquatic Areas

Manually 

Pressurized 

Handwand

63 0.018 0.000092 lb 

ai/ft2 500 ft2 0.00011 28,000 0.00001 160

Backpack Sprayer 130 0.14 0.000092 lb 

ai/ft2 500 ft2 0.00022 13,000 0.000081 21

Bolded values are below the LOC (100 for dermal and 30 for inhalation) and represent risks of concern.

1. Application rates primarily based on use information provided by registrant (supplied by email from PRD 9/5/2014). The use 

information provided was noted to be based primarily on representative Section 3 and 24C labels from Syngenta Crop 

Protection. In addition, information provided in the TRED (D281890) for diquat was used for the residential use information.

2. Based on the HED’s SOPs for Residential Pesticide Exposure Assessment; Lawns/Turf (Feb. 2012) and Aquatic SOP.

3. Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/area treated or amount handled) x Area treated or 

amount handled * absorption factor (inhalation = 0.3%) / body weight (80 kg).

4. Dermal MOE = NOAEL (3 mg/kg/day) / daily dose (mg/kg/day). LOC= 100.

5. Inhalation Dose = daily unit exposure (mg/lb ai) x application rate (lb ai/area treated or amount handled) x Area treated or 

amount handled / body weight (80 kg).

6. Inhalation MOE = Human-equivalent dose (0.0017 mg/kg/day) / daily dose (mg/kg/day). LOC = 30.

6.2 Residential Post-Application Exposure

There is the potential for post-application exposure for individuals exposed as a result of being in 

an environment that has been previously treated with diquat. The quantitative exposure/risk 

assessment for residential post-application exposures is based on the following scenarios: 

Lawns and Turf:

 High-contact activities, mowing, and golfing [used on resistant dormant turf (Bermuda

grass and Zoysia grass) for weed control].

 Incidental oral: hand-to-mouth (HtM), object-to-mouth (OtM), and soil ingestion (SI)

Gardens and Trees:

 Garden activities

Aquatic Activities:

 Swimming

A series of assumptions and exposure factors served as the basis for completing the residential 

post-application risk assessments. Assumptions and factors, as well as algorithms used to 

estimate non-cancer exposure and dose for residential post-application are detailed in the most 

recent ORE assessment memo (J. Miller; 17-SEP-2015; D427297). 
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The incidental oral scenarios (i.e., HtM and OtM) should be considered inter-related and it is 

likely that they occur interspersed amongst each other across time. Combining these scenarios 

with the dermal exposure scenario would be overly-conservative because of the conservative 

nature of each individual assessment. Therefore, the post-application exposure scenario with the 

highest exposure (HtM) was combined with dermal exposures for children 1 < 2 years old. The 

residential post-application exposures are summarized in Table 6.2.1. All combined dermal and 

incidental oral MOEs are ≥ 100.

Table 6.2.1. Residential Post-application Non-cancer Exposure and Risk Estimates for Diquat.

Lifestage

Post-application Exposure Scenario Application 

Rate1

Dose 

(mg/kg/day)2 MOEs3

Combined Routes

(X indicates 

included in 

Combined MOE)

Combined 

MOEs4

Use Site Route of Exposure / 

Activity

Adult

Lawns and 

Turf

Dermal / High-Contact 

Activities

0.5 lb 

ai/Acre

0.00060 5,300 N/A

N/A Dermal / Mowing 0.000012 260,000 N/A

Dermal / Golfing 0.000044 68,000 N/A

Child

1 to < 2 

years old

Dermal / High-Contact 

Activities 0.0011 2,700

X 350 Incidental Oral / Handto-Mouth 0.0076 390

Incidental Oral / Objectto-Mouth 0.00023 13,000 N/A

N/A

Incidental oral / Soil 

Ingestion 1.7E-05 180,000 N/A

Child

11 to < 16 

years old

Lawns and 

Turf

Dermal / Mowing

0.5 lb 

ai/Acre

0.000013 230,000 N/A

N/A

Child

11 to < 16

Years old

Dermal / Golfing

0.00052 58,000 N/A

Child

6 to < 11 

Years old 

0.000060 50,000 N/A

N/A Adult Gardens General Activities 0.00096 31,000

Child N/A

6 < 11 

years

Gardens General Activities 0.00070 4,600

Adult

Aquatic

(swimming)

Inhalation

0.000092 lb 

ai/ft 2

2.42E-12 7.00E+08 N/A 7.00E+08

Dermal 2.23E-09 1.30E+09

X 4.20E+05

Ingestion 7.20E-06 4.20E+05

Child

3 to < 6 

years old

Inhalation 2.67E-12 6.40E+08 N/A 6.40E+8

Dermal 1.47E-09 2.00E+09

X 2.50E+05

Ingestion 1.2E-05 2.50E+05

1 Application rates primarily based on use information provided by the registrant (supplied by email from PRD 9/5/2014). The use information 

provided was noted to be based primarily on representative Section 3 and 24C labels from Syngenta Crop Protection. In addition, information 

provided in the TRED (D281890) for diquat was used for the residential use information.

2 Dose (mg/kg/day) equations provided in Appendix A of the most recent ORE memo (J. Miller; 17-SEP-2015; D427297). 
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3 MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day).

4 Combined MOE = POD (3 mg/kg/day) / (dermal dose + incidental oral dose).

6.3 Residential Risk Estimates for Use in Aggregate Assessment

There were certain residential handler scenarios with risks of concern for inhalation using 

backpack sprayer applications (LOC < 30). Since these scenarios represent risks of concern 

alone, they are not used in aggregate assessment (i.e., these scenarios will also be of concern for 

aggregate). Only the residential exposure scenarios that were not of concern (MOE ≥ 100 for 

dermal and incidental oral and 30 for inhalation) are included in the aggregate assessment.

Table 6.3.1 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for diquat:

 The recommended residential exposure for use in the adult aggregate assessment reflects 

dermal and inhalation exposure from mixing/loading/applying a (SC) liquid with a 

manually pressurized handwand to turf, gardens, and trees.

 The recommended residential exposure for use in the children 1 to 2 years old aggregate 

assessment reflects high-contact activity exposures from post-application exposure to 

outdoor treated turf. This lifestage is the most highly exposed population for this 

exposure scenario; therefore, it is considered protective of the other lifestages.

 The recommended residential exposure for use in the children 3 to 6 years old aggregate 

assessment reflects post-application exposure from swimming in treated areas. This 

lifestage is the most highly exposed population for this exposure scenario; therefore, it is 

considered protective of the other lifestages.

Table 6.3.1. Recommendations for the Residential Exposures for the Diquat Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE2

Dermal Inhalation Oral Total3

(dermal + oral)

Dermal

(LOC 

=100)

Inhalation

(LOC = 

30)

Oral Total3,4

(dermal + oral)

Adult

Handler: 

Manually 

Pressurized 

Handwand 

Sprayer 

Treating 

Turf/Gardens/

Trees

0.00012 0.000011 N/A N/A 25,000 150 N/A N/A

Child 

1 to 2 years 

old

High-contact 

Activities 

from Treated 

Turf

0.0011 N/A 0.0076 0.0087 2,700 N/A 390 350

Child

3 to < 6 

years old 

Aquatic 

(swimming) 1.47E-09 2.67E-12 1.2E-05 1.20E-5 2.00E+09 6.40E+08 2.50E+05 2.50E+05

1. Dose = the highest dose for each applicable lifestage of all residential scenarios assessed (that was not of concern). 

2. MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day).

3. Inhalation endpoint is based on a different study with different effects thus not combined with the other routes. Therefore, total = dermal + 

incidental oral (where applicable).

4. Total MOE = [3.0 mg/kg/day / (Combined dermal + oral dose)], where applicable.
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6.4 Residential Bystander Post-Application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its FIFRA Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 20105. The Agency has 

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis6. During Registration Review, the Agency will utilize this 

analysis to determine if data (i.e., flux studies, route-specific inhalation toxicological studies) or 

further analysis is required for diquat.

6.5 Spray Drift

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g., children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling onto 50-feet wide lawns 

coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.7 Direct exposures would include inhalation of the spray plume or being sprayed 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (1 to 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

Several diquat products have existing labels for use on turf, thus it was considered whether the 

risk assessment for that use may be considered protective of any type of exposure that would be 

associated with spray drift. It should be noted that the registered residential uses on turf result in 

exposure greater than potential exposure from spray drift; therefore, no new residential 

assessment needs to be completed. If the maximum application rate on crops adjusted by the 

amount of drift expected is less than or equal to existing turf application rates, the existing turf 

assessment is considered protective of spray drift exposure. The currently registered maximum 

single application rate of diquat for crops is (0.5 lb ai/A). The highest degree of spray drift noted 

for any application method immediately adjacent to a treated field (Tier 1 output from the aerial 

application using fine to medium spray quality) results in a deposition fraction of 0.26 of the 

application rate. A quantitative spray drift assessment for diquat is not required because the 

maximum application rate to a crop/target site multiplied by the adjustment factor for drift of 

0.26 is less than the maximum direct spray residential turf application rate (0.5 lb ai/A)8for any

 

5 http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

6 http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219

7 This approach is consistent with the requirements of the EPA’s Worker Protection Standard.

8 0.5 lb ai/A x 0.26 ≤ 0.5 lb ai/A
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diquat products. The turf post-application MOEs have been previously assessed and are based 

on the revised SOPs for Residential Exposure Assessment (see Section 6.2).

For aquatic uses, subsurface, bottom placement, and surface applications (by aerial or handheld 

equipment) may be made. Of the three applications, the only application with the potential for 

spray drift is surface application as a spray. Although the label does not prohibit the use of aerial 

applications for aquatic areas, it is unlikely aerial applications would be made given the types of 

water bodies the product is being applied to and the alternative application options (handheld 

application equipment). Clarification should be added to aquatic use labels regarding whether 

aerial applications are allowed. 

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, the HED must consider and aggregate (add) pesticide exposures 

and risks from three major sources: food, drinking water, and residential exposures. In an 

aggregate assessment, exposures from relevant sources are added together and compared to 

quantitative estimates of hazard (e.g. a NOAEL or PAD), or the risks themselves can be 

aggregated. When aggregating exposures and risks from various sources, both the route and 

duration of exposure are considered.

For diquat, aggregate exposure and risk assessments were assessed for the following scenarios: 

acute aggregate exposure, short- and intermediate-term aggregate exposure, and chronic 

aggregate exposure. Diquat is classified as “Category E – evidence of non-carcinogenicity to 

humans”; therefore, a cancer aggregate risk assessment was not performed.

7.1 Acute Aggregate Risk

The acute aggregate risk is equivalent to the acute dietary risk estimates. The acute dietary 

exposure estimates are not of concern (<100% aPAD) for the general U.S. population and all 

population subgroups (see Section 5.4).

7.2 Short- and Intermediate-Term Aggregate Risk

Short-term (1 to 30 day) and intermediate-term (1 to 6 months) aggregate risk assessments are 

necessary since there is potential for post-application exposure from the uses of diquat in 

residential settings. Since the short-term assessment assumed no dissipation (i.e., day-zero 

residues) for the entire exposure duration (up to 30 days), and the short- and intermediate-term 

PODs are the same, the short-term assessment is expected to be protective of intermediate-term 

exposure durations. 

Several scenarios were of concern based on residential handler risk from inhalation exposure 

alone (see Section 6.1); therefore, these scenarios cannot be used in the aggregate assessment. 

Table 7.2.1 presents short- and intermediate-term aggregate risk calculations using worst-case

residential scenarios that were not of concern. Aggregate MOEs were not of concern for these 

scenarios (i.e., MOEs ≥ 100).
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Table 7.2.1. Short- and Intermediate-Term Aggregate Risk Calculations.

Population

Short- or Intermediate-Term Scenario

NOAEL 

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average 

Food and 

Water 

Exposure 

mg/kg/day3

Residential 

Exposure 

mg/kg/day4

Total 

Exposure 

mg/kg/day5

Aggregate 

MOE (food, 

water, and 

residential)6

Adult3 3 100 0.03 0.000745 0.00012 8.65E-4 3400

Child

1 to 2 years old 3 100 0.03 0.001673 0.0087 0.01037 290

Child

3 to < 6 years old 3 100 0.03 0.001387 1.2E-5 0.00140 2100

1 LOC = 100 (10X intraspecies UF, 10X interspecies UF, and 1X FQPA SF).

2 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC.

3 Values taken from Table 5.4.1 for the appropriate population subgroup. For adults, the most highly exposed adult population 

subgroup was adults 20-49 years old. 

4 Residential Exposure = [Oral exposure + Dermal exposure]. Inhalation endpoint is based on a different study with different 

effects thus not combined. See Table 6.3.1 for recommended values for aggregate assessment.

5 Total Exposure = Avg. Food & Water Exposure + Residential Exposure.

6 Aggregate MOE = [NOAEL / (Avg. Food & Water Exposure + Residential Exposure)].

7.3 Chronic Aggregate Risk

There are no chronic residential exposure scenarios; therefore, the chronic aggregate risk is

equivalent to the chronic dietary risk estimate. The chronic dietary exposure estimates are not of 

concern (<100% cPAD) for the general U.S. population and all population subgroups (see 

Section 5.4).

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to diquat and any other substances and diquat does not appear to produce a toxic metabolite 

produced by other substances. For the purposes of this tolerance action, therefore, EPA has not 

assumed that diquat has a common mechanism of toxicity with other substances. For 

information regarding EPA’s efforts to determine which chemicals have a common mechanism 

of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements 

released by EPA’s OPP concerning common mechanism determinations and procedures for 

cumulating effects from substances found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

9.1 Short-/Intermediate-Term Handler Risk

The HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. There are distinct job functions or tasks related to applications and 

exposures can vary depending on the specifics of each task. Job requirements (the amount of 

chemical used in each application), the kinds of equipment used, the target being treated, and the 

level of protection used by a handler can cause exposure levels to differ in a manner specific to 

each application event. 
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Based on the anticipated use patterns and current labeling, occupational handler exposure is 

expected from the registered uses of diquat. The quantitative exposure/risk assessment 

developed for occupational handlers is based on the following scenarios:

 Mixing/loading for aerial application on typical and high-acreage crops and aquatic areas; 

 Mixing/loading for groundboom application on typical and high-acreage crops, turf (golf 

courses), orchard/vineyard crops, and aquatic areas; 

 Applying via aerial equipment on typical and high-acreage crops, and aquatic areas;

 Applying via groundboom on turf (golf course), field grown ornamentals, orchards, 

greenhouses, typical and high-acreage field crops, and aquatic areas; 

 Applying via mechanically pressurized handgun on rights of way/industrial areas;

 Applying via trigger-spray bottle on foundations/perimeters, landscaping and turf (lawns, 

athletic fields, parks, etc.);

 Mixing/loading/applying via a backpack sprayer for orchard/vineyards, greenhouse use, 

rights-of ways, landscaping, turf, structural areas (bridges, shipyards);

industrial/commercial areas, foundations/perimeter, and aquatic areas (lakes/ponds);

 Mixing/loading/applying for a manually pressurized handwand for use in greenhouses, 

turf (lawns, athletic fields, parks, etc.), rights of way/industrial areas, 

foundations/perimeters, and aquatic areas (lakes, ponds, etc.);

 Mixing/loading/applying via mechanically pressurized handgun for orchards (in and 

around trees), greenhouses, turf (golf courses), landscaping and turf (lawns, athletic 

fields, parks, etc.), industrial/commercial areas, typical field crops and aquatic areas 

(lakes/ponds); and

 Flagger for typical and high-acreage field crops.

A series of assumptions and exposure factors served as the basis for completing the occupational 

handler risk assessments. Assumptions and factors, as well as algorithms used to estimate noncancer exposure and dose for occupational handlers, are detailed in the most recent ORE 

assessment memo (J. Miller; 17-SEP-2015; D427297). Based on the registered uses, short-, and 

intermediate-term exposures are expected for the following reasons: (1) type of application 

method (aquatic, ground directed defoliant/desiccant), and (2) maximum number of applications 

per year (2).

Estimates of dermal and inhalation exposure were calculated for various levels of PPE. The 

diquat product labels direct mixers, loaders, applicators and other handlers to wear long-sleeved 

shirt and long pants, coveralls, shoes plus socks, chemical-resistant gloves, and protective 

eyewear such as goggles or face shield, chemical-resistant headgear for overhead exposure, 

chemical-resistant apron when cleaning equipment, and no respirator. 

The occupational handler non-cancer exposure and risk estimates for diquat are summarized in 

Table 9.1.1. There are no dermal short- or intermediate-term occupational risk estimates of 

concern when handlers use label-specific PPE for the existing uses of diquat (i.e., MOEs ≥ 100). 

Some occupational scenarios reached acceptable inhalation MOEs (MOEs ≥ 30) at 

baseline/label-specific PPE (i.e., no respirator); however, several exposure scenarios presented 

risk estimates of concern (MOE <30) at baseline/label-specific PPE. Risk estimates were 

calculated for these scenarios using additional PPE or engineering controls. 

The following scenarios reached acceptable MOEs with the addition of a PF5 respirator:

 Mixing/loading for aerial applications to typical-acreage crops and aquatic areas;
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 Mixing/loading for groundboom applications to high-acreage crops and aquatic areas; 

 Applying with groundboom on turf (golf course), field-grown ornamentals, orchards, 

aquatic areas, and typical-acreage field crops;

 Applying with mechanically pressurized handgun on rights of way/industrial areas;

 Mixing/loading/applying for a mechanically pressurized handgun application for use in 

orchards (in and around trees), industrial/commercial areas, and typical field crops; and

 Flagger for typical- and high-acreage field crops.

The following scenarios reached acceptable MOEs with the addition of a PF10 respirator:

 Mixing/loading for aerial applications to high-acreage crops and aquatic areas;

 Applying with groundboom to high-acreage field crops and aquatic areas; and

 Mixing/loading/applying for a mechanically pressurized handgun application in 

lakes/ponds.

The following scenarios reached acceptable MOEs with the addition of engineering controls

(enclosed cab):

 Applying with groundboom to aquatic areas.

The following scenarios do not reach acceptable MOEs even with maximum PPE (engineering 

controls cannot be utilized for hand-held equipment):

 Mixing/loading/applying for a mechanically pressurized handgun application in 

greenhouses.

Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Diquat.

Exposure 

Scenario

Crop

or 

Target

Mitigation 

Level

Mitigation 

Level Max.

App.

Rate2

Area 

Treated 

or 

Amount 

Handled 

Daily3

Dermal Inhalation

Dermal

Unit 

Exposure 

(μg/lb ai)1

Inhalation 

Unit

Exposure 

(μg/lb ai)1

Dose 

(mg/kg/day)4

MOE5

LOC = 100

Dose 

(mg/kg/day)6

MOE7

LOC = 30

Mixer/Loader (SC)

Aerial

Field Crop/8

Typical

Label10

29.1

Label

0.219

0.5 lb 

ai/acre

350 0.00019 16,000

Label

0.000479 11

Mitigation9

PF 5

0.0438

Mitigation PF 

5

0.0000959

53

Field Crop, Highacreage 

(Canola/

Potato -

Pre-harvest)

Label

0.219

1200 0.00066 4,600

Label

0.00164 3.1

Mitigation9

PF 5

0.0438

Mitigation9

PF 5

0.0438

16

Mitigation 

PF 10

0.0219

Mitigation PF 

10

0.000164

31

Aquatic Areas 

(lakes, ponds, etc.)

Label

0.219

Mitigation 

PF 10

0.0219

4 lb 

ai/acrefeet

120 acrefeet 0.00053 5,700

Label

0.00131

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

Mitigation

PF 10

0.000131

3.9

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

39 Groundboom Aquatic Areas 

(lakes, ponds, etc.)

Label

29.1
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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Diquat.

Exposure 

Scenario

Crop

or 

Target

Mitigation 

Level

Mitigation 

Level Max.

App.

Rate2

Area 

Treated 

or 

Amount 

Handled 

Daily3

Dermal Inhalation

Dermal

Unit 

Exposure 

(μg/lb ai)1

Inhalation 

Unit

Exposure 

(μg/lb ai)1

Dose 

(mg/kg/day)4

MOE5

LOC = 100

Dose 

(mg/kg/day)6

MOE7

LOC = 30

Golf Course 

(fairways, tees, 

greens)

Label

0.219

0.5 lb 

ai/acre

40 0.000022 140,000 Label

0.0000548 93 Field-grown 

Ornamental

Crops

Orchard/

Vineyard

Field Crop/

Typical 80 0.000044 69,000 Label0.000479 46

Field Crop,

High-acreage

Label

0.219

200 0.00011 28,000

Label

0.0219 19

Mitigation 

PF 5

0.0438

Mitigation 

PF 5

0.00438

93

Applicator

Aerial

Field crop/

Typical

EC

2.08

EC

0.0049

0.5 lb 

ai/acre

350 EC

0.000014

EC

220,000 0.000011 230

Field Crop,

High-acreage

1200 EC

0.000047

EC

64,000 0.000037 68

Aquatic Areas 

(lakes, ponds, etc.)

EC

2.08

4 lb 

ai/acrefeet

120 acrefeetEC

0.000037

EC

80,000

EC

0.000029 85

Groundboom

Golf Course 

(fairways, tees, 

greens)

Field-grown 

Ornamental 

Crops

Orchard/

Vineyard

Label

12.6

Label

0.34

0.5 lb 

ai/acre

40 0.0000095 320,000

Label

0.000085 29

Mitigation 

PF 5

0.068

Mitigation

PF 5

0.000017

150

Field Crop, 

Typical

Label

0.34

80 0.000019 160,000

Label

0.000085 15

Mitigation 

PF 5

0.068

Mitigation

PF 5

0.000034

74

Field Crop,

High-acreage

Label

0.34

200 0.000047 63,000

Label

0.00043

5.9

Mitigation 

PF 5

0.068

Mitigation

PF 5

0.000085

29
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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Diquat.

Exposure 

Scenario

Crop

or 

Target

Mitigation 

Level

Mitigation 

Level Max.

App.

Rate2

Area 

Treated 

or 

Amount 

Handled 

Daily3

Dermal Inhalation

Dermal

Unit 

Exposure 

(μg/lb ai)1

Inhalation 

Unit

Exposure 

(μg/lb ai)1

Dose 

(mg/kg/day)4

MOE5

LOC = 100

Dose 

(mg/kg/day)6

MOE7

LOC = 30

Mitigation 

PF 10

0.034

Mitigation

PF 10

0.000043

59

Aquatic Areas 

(lakes, ponds, etc.)

Label

0.34

4 lb 

ai/acrefeet

120 acrefeet 0.000092 33,000

Label

0.0020 1.2

Mitigation 

PF 10

0.034

Mitigation 

PF 10

0.00020

12

EC

0.043

EC

0.00026 34

Mechanically 

Pressurized 

Handgun

Rights-of-way 

(e.g., utilities, 

Railroad, 

Roadways

Label

290

Label

3.9

0.01 lb 

ai/gal

1,000

gal 0.00011 28,000

Label

0.000488 18

Mitigation 

PF 5

0.078

Mitigation

PF 5

0.000098

90

Trigger-Spray 

bottle

(R-T-U)

Foundations/

Perimeter

Label

11100

Label

61.2

0.0045

lb 

ai/bottle

2

bottles 0.00000021 14,000,000 0.0000038 1,300 Landscaping, Turf 

(lawns, athletic 

fields, parks, etc.)

Flagger (SC)

Aerial

Field Crop/

Typical

and

High-acreage

Label

10.6

Label

0.35 0.5 350 0.000070 43,000

Label

0.000766 11

Mitigation

PF 5

0.000154

57

Mixer/Loader/Applicator (SC)

Backpack

Sprayer

Orchard/

Vineyard

(Ground/soildirected)

Label

4120

Label

2.58

0.01

lb ai/gal

40 gal

0.000062 48,000 0.0000129 400

Rights-of-way 

(e.g., utilities, 

railroad, 

roadways)

Landscaping, Turf 

(lawns, athletic 

fields, parks, etc.)

Spot Treatment

Foundations/

Perimeter

Aquatic Areas 

(lakes, ponds, etc.)

0.04 lb 

ai/gal 0.00025 6,100 0.0000516 99
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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Diquat.

Exposure 

Scenario

Crop

or 

Target

Mitigation 

Level

Mitigation 

Level Max.

App.

Rate2

Area 

Treated 

or 

Amount 

Handled 

Daily3

Dermal Inhalation

Dermal

Unit 

Exposure 

(μg/lb ai)1

Inhalation 

Unit

Exposure 

(μg/lb ai)1

Dose 

(mg/kg/day)4

MOE5

LOC = 100

Dose 

(mg/kg/day)6

MOE7

LOC = 30

Structural (e.g., 

bridges, shipyards, 

home decks, 

foundations) Label

1600

Label

30

0.01

lb ai/gal 0.000024 130,000 0.00015 59

Industrial/

Commercial (tires, 

rail yards, junk 

yards, etc.)

Manuallypressurized 

Handwand

Greenhouse 

(ornamentals, 

roses, cut flowers, 

container stock, 

vegetables)

Label

365

Label

30

0.01 lb 

ai/gal

40 gal

0.0000055 550,000 0.00015 59

Landscaping, Turf 

(lawns, athletic 

fields, parks, etc.)

Industrial/

Commercial 

Foundations/

Perimeter

Structural (e.g., 

bridges, shipyards, 

home decks, 

foundations)

Aquatic Areas 

(lakes, ponds, etc.) 

Label

365

Label

30 0.04 lb 

ai/gal 0.000022 140,000

Label

0.0006 15

Mitigation 

PF5

6

Mitigation

PF 5

0.00012

73

Mechanicallypressurized 

Handgun

Orchard/

Vineyard

Drench/Soil-

/Ground-directed

Industrial/

Commercial/

Field crop, Typical

Label

290

Label

3.9

0.01 lb 

ai/gal 1000 gal

0.00011 28,000

Label

0.000488 18

Mitigation 

PF 5

0.078

Mitigation

PF 5

0.000098

90

Greenhouse 

(ornamentals, 

roses, cut flowers, 

container stock, 

vegetables)

Drench/Soil-

/Ground-directed

Label

1,600

Label

120

0.00060 5,000

Label

0.015 0.59

Mitigation

PF 5

24

Mitigation

PF 5

0.003

2.9

Mitigation

PF 10

12

Mitigation

PF 10

0.0015

5.9

Golf Course 

(fairways, tees, 

greens)

Label

450

Label

1.9

0.5 lb 

ai/Acre 5 acres 0.000042 71,000 0.0000594 86
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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Diquat.

Exposure 

Scenario

Crop

or 

Target

Mitigation 

Level

Mitigation 

Level Max.

App.

Rate2

Area 

Treated 

or 

Amount 

Handled 

Daily3

Dermal Inhalation

Dermal

Unit 

Exposure 

(μg/lb ai)1

Inhalation 

Unit

Exposure 

(μg/lb ai)1

Dose 

(mg/kg/day)4

MOE5

LOC = 100

Dose 

(mg/kg/day)6

MOE7

LOC = 30

Landscaping, Turf 

(lawns, athletic 

fields, parks, etc.)

Aquatic Areas 

(lakes, ponds, etc.)

Label

290

Label

3.9

0.04 lb 

ai/gal 1000 gal 0.00044 6,900

Label

0.00195 4.5

Mitigation 

PF 5

0.078

Mitigation

PF 5

0.00039

23

Mitigation 

PF 10

0.39

Mitigation

PF 10

0.000195

45

Bolded values are below the LOC (100 for dermal and 30 for inhalation).

1. Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (2013); Level of mitigation: Label specific and PPE-

(respirator). 

2. Based on Appendix E.

3. Exposure Science Advisory Council Policy #9.0., draft Aquatic SOP September 2013.

4. Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or 

Amount Handled Daily (A or gal/day) × DAF (0.3 %) ÷ BW (80 kg).

5. Dermal MOE = Dermal NOAEL (3 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6. Inhalation Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or 

Amount Handled Daily (A or gal/day) ÷ BW (80 kg).

7. Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). NOAEL = 0.0025, 0.0051, 0.0088 mg/kg/day for 

breathing rates of 8.3, 16.7, and 29 L/min, respectively.

8. Field Crop/Typical: carrots, coriander, radishes, spinach, sugar beets, table beets, turnips, calendula, tomato vines, cantaloupe vines, 

cucumbers, squash, watermelon vines, acorn squash, peppers, eggplant, green pepper, tomato, green peppers, tomatoes.

9. Mitigation: Level of PPE above what is currently required on the labels needed to achieve a MOE = 30 for inhalation exposure.

10. The diquat product labels direct mixers, loaders, applicators and other handlers to wear long-sleeved shirt and long pants, coveralls, shoes 

plus socks, chemical-resistant gloves and protective eyewear such as goggles or face shield, chemical-resistant headgear for overhead 

exposure, chemical-resistant apron when cleaning equipment and no respirator.

9.2 Occupational Post-Application Exposure

The HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. In the case of post-harvest treatment, post-application activities include sorting 

and packing the treated crop. Post-application exposure levels vary over time and depend on 

such things as the type of activity, the nature of the crop or target that was treated, the application

method, and the chemical’s degradation properties. 

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and re-suspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on March 
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2, 20109. The Agency has evaluated the SAP report and has developed a Volatilization 

Screening Tool and a subsequent Volatilization Screening Analysis10. During Registration 

Review, the Agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for diquat.

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the Agency's risk assessments.

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

Due to the nature of the chemical (desiccant/defoliant herbicide) and the exposure scenarios (preand post-harvest for the control of weeds and aquatic uses), a quantitative occupational postapplication dermal exposure assessment was not warranted for most diquat use patterns. 

However, a dermal post-application assessment was completed for the registered golf course turf 

uses to address exposure to workers performing maintenance activities on golf courses after the 

application of diquat since diquat can be applied to dormant turf to control weeds and nuisance 

grasses in certain seasons. 

A series of assumptions and exposure factors served as the basis for completing the occupational 

post-application risk assessment. Each assumption and factor is detailed in the most recent ORE 

memo (J. Miller; 17-SEP-2015; D427297). Chemical-specific dislodgeable foliar residue "turf" 

data have been submitted for diquat; however, the Agency-preferred method (the modified 

California roller method) was not used for data gathering. This assessment uses HED’s default 

assumption that 1% of the application is available for transfer on day 0 following the application 

and the residues dissipate at a rate of 10% each following day. Post-application dermal MOEs 

were not of concern (i.e., MOEs ≥ 100).

Table 9.2.2.1. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Diquat.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR/TTR1 Dermal Dose (mg/kg/day)2 MOE3

Short- and Intermediate-Term

Turf:

Golf Course

Maintenance 3700

0.056

0.000062 48,000

Maintenance/greens 

only 2500 0.000042 71,000

1 TTR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.1 and D = 0.10 per day.

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (0.3 %)]  BW (80 kg).

3 MOE = POD (3 mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR/TTR (μg/cm2) × TC × 0.001 mg/μg × 8 hrs/day × DAF (0.3 

%)]  BW (80 kg).

Restricted-Entry Interval (REI)

Diquat exhibits low acute toxicity via the oral (Toxicity Category II for technical, III for 

formulation) and inhalation (Toxicity Category III) routes of exposure but is moderately-toseverely toxic via the dermal route of exposure (Toxicity Categories I for technical and II for 

formulation). Diquat is not an acute skin irritant (Toxicity Category IV) nor a dermal sensitizer, 

 

9 http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

10 http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219
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but it is considered a moderate-to-severe eye irritant (Toxicity Category II). Although short- and 

intermediate-term post-application risk estimates were not of concern on day 0 (12 hours after 

application) for any post-application activities, the appropriate REI is based on acute toxicity via 

the dermal route of exposure (Toxicity Categories I for technical and II for formulation). 

Accordingly, HED recommends an REI of 48 hours per 40 CFR 156.208 (c) (2) (i). The current 

product labels require a 24-hour REI.

cc: M. Perron, G. Kramer, J. Miller

RDI: RAB1 (17-SEP-2015) 

M.M. Perron:S10955:PY-S:(703)347-0395:7509P:RAB1
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Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

Study requirements (40 CFR 158.340) for diquat are presented below. Use of the new guideline 

numbers does not imply that the new (1998) guideline protocols were used.

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Acute Eye Irritation.......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity (rodent) ......................................

870.3150 90-Day Oral Toxicity (nonrodent) ................................

870.3200 21/28-Day Dermal Toxicity ..........................................

870.3250 90-Day Dermal Toxicity ...............................................

870.3465 90-Day Inhalation Toxicity ...........................................

no1

no2

yes

no

yes

--

--

yes

--

yes

870.3700a Prenatal Developmental Toxicity (rodent) ....................

870.3700b Prenatal Developmental Toxicity (nonrodent) ..............

870.3800 Reproduction and Fertility Effects ................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse) ...............................................

870.4300 Combined Chronic Toxicity/Carcinogenicity ...............

yes

yes

yes

yes

yes

yes3

yes

yes3

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test..

870.5xxx Mutagenicity— Structural Chromosomal Aberrations..

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6200a Acute Neurotoxicity Screening Battery (rat).................

870.6200b 90-Day Neurotoxicity Screening Battery (rat) ..............

870.6300 Developmental Neurotoxicity .......................................

yes

yes

no

yes

yes

--

870.7485 Metabolism and Pharmacokinetics................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

yes

yes

yes

yes

yes

1 Subchronic exposure in the rat has been evaluated in the subchronic neurotoxicity study, prenatal developmental 

toxicity study, and as part of the combined chronic toxicity/carcinogenicity study. Therefore, a study is not required 

at this time.

2 A subchronic dog study is not needed given a chronic dog study was submitted.

3 The combined chronic toxicity/carcinogenicity study satisfies the requirement of the study. 
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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile – Diquat.

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 00081506 LD50 = 810 mg/kg 

LD50 = 600 mg/kg III

870.1200 Acute dermal (rabbit) 00100614

LD50 = 262 mg/kg 

LD50 = 315 mg/kg

LD50 = 288.5 mg/kg

II

870.1300 Acute inhalation (rat) Accession No. 

26385

LC50 = 0.80 mg/L

LC50 = 1.09 mg/L

LC50 = 0.97 mg/L

III

870.2400 Acute eye irritation (rabbit) 00081507 Slight to severe eye 

irritant II

870.2500 Acute dermal irritation (rabbit) 00107903 Slight irritation IV

870.2600 Skin sensitization (guinea pig) 00107903 Not a dermal sensitizer N/A

With the exception of the dermal sensitization study, which was conducted with the technical diquat (Diquat Herbicide 

Concentrate), the above studies were conducted with the end-use products [Diquat Water Weed Killer and Diquat 2 Spray (eye 

irritation study only)] and not in terms of the diquat ion. Because the only difference between the technical diquat and the enduse products is 2.15% water, studies with the end-use products have been accepted to satisfy the generic data requirements for 

acute studies. The above LD and LC values are expressed in terms of the test material and no, as is commonly done with diquat, 

in terms of the diquat cation.

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile – Diquat.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification/Doses Results

870.3200 21/28-Day Dermal 

Toxicity (rat)

Technical (20.64% 

diquat cation)

40308101 (1987)

Acceptable/guideline

0, 5, 20, 40, or 80 mg/kg/day

Dermal Toxicity NOAEL <5 mg/kg/day.

Dermal Toxicity LOAEL = 5 mg/kg/day, based on 

dermal irritation at application site [erythema, 

edema, atonia, and desquamation] and tissue 

destruction [necrosis and eschar formation].

Systemic Toxicity NOAEL = 5 mg/kg/day.

Systemic Toxicity LOAEL = 20 mg/kg/day, based 

on a dose-related mortality and clinical signs 

[hypothermia, hypoactivity, dyspnea, cyanosis, pale 

extremities, general poor condition, and emaciated 

appearance]. Based on the severity of the effects 

observed [death and clinical signs (hypothermia, 

hypoactivity, dyspnea, cyanosis, pale extremities, 

general poor condition, and emaciated appearance)] 

and the extent of skin toxicity [dermal irritation 

(erythema, edema, and desquamation) and tissue 

destruction (necrosis and eschar formation); sores, 

severe erythema, fissures, acute necrotizing 

purulent dermatitis, and degeneration of the hair 

follicles and sebaceous glands] observed at the site 

of application in one or both sexes, it was 

concluded that the study was not appropriate for use 

in risk assessment since the NOAEL is artificially 

low due to the fact that the skin is compromised.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile – Diquat.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification/Doses Results

870.3200 21/28-Day Dermal 

Toxicity (rabbit)

Technical

00140576 (1966)

Acceptable/non-guideline

0, 20, 40, 80, or 160 diquat 

cation mg/kg/day

Dermal Toxicity NOAEL = <20 mg/kg/day.

Dermal Toxicity LOAEL = 20 mg/kg/day, based on 

erythema and scabbing.

Systemic Toxicity NOAEL = 20 mg/kg/day.

Systemic LOAEL = 40 mg/kg/day, based on weight 

loss, unsteadiness, muscular weakness and inability 

to stand, and pathological changes in the distal 

convoluted renal tubules with cell necrosis (thought 

to be associated with an electrolyte imbalance).

Extensive areas of necrosis of the epidermis were 

noted.

870.3465 Subchronic

Inhalation Study 

(rat) – 21 days

Technical (21.6% 

and 23.5% diquat 

cation)

40301701, 40640801 (1987)

Acceptable/guideline (when 

both studies considered 

together)

0, 0.49, 1.1, 3.8 μg/L; 0 and 

0.1 μg/L

NOAEL = 0.1 μg/L/day [males 0.024 mg/kg/day; 

females 0.026 mg/kg/day], based on increased lung 

weights and microscopic lesions [mottling and 

reddening of the lungs in females, multifocal, 

chronic, interstitial pneumonia, and alveolar 

macrophages in both sexes] in the lungs at the 

LOAEL of 0.49 μg/L [males 0.117 mg/kg/day; 

females 0.128 mg/kg/day].

870.3700a Prenatal 

Developmental in 

Rodent (rat)

Technical (26.2% 

diquat cation)

41198902 (1989)

Acceptable/guideline

0, 4, 12, or 40 mg/kg/day

Maternal NOAEL = 12 mg/kg/day.

Maternal LOAEL = 40 mg/kg/day based on death 

of one dam, increased incidence of subdued 

appearance and piloerection, and a slightly lower 

gravid uterine weight.

Developmental NOAEL = 12 mg/kg/day.

Developmental LOAEL = 40 mg/kg/day based on 

decreased fetal body weight (91% of control), 

decreased litter weight, an increased incidence of 

hemorrhagic kidney, and poor ossification as 

evidenced by higher incidences of minor skeletal 

alterations compared to controls.

870.3700a Prenatal 

Developmental in 

Rodent (mouse)

Analytical standard

00061637 (1978)

Unacceptable/non-guideline

0, 1, 2, or 4 mg/kg/day Poor dosing technique/intubation errors resulting in 

incidental exposure into lungs.

870.3700b Prenatal 

Developmental in 

Non-Rodent (rabbit)

Technical (26.2% 

diquat cation)

41198901 (1989)

Acceptable/guideline

0, 1, 3, or 10 mg/kg/day

Maternal NOAEL = 3 mg/kg/day.

Maternal LOAEL = 10 mg/kg/day based on 

mortality and an increased incidence of clinical 

signs (diarrhea, subdued appearance, and thin 

appearance).

Developmental NOAEL = 3 mg/kg/day.

Developmental LOAEL = 10 mg/kg/day based on 

an increased incidence of friable and/or mottled 

livers and poorer ossification, as evidenced by 

minor skeletal alterations.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile – Diquat.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification/Doses Results

870.3800 Reproduction and 

Fertility Effects (rat)

Technical (20.09% 

diquat cation)

41531301 (1990)

Acceptable/guideline

0, 0.8, 4, or 20/12 mg/kg/day

Parental NOAEL = 0.8 mg/kg/day.

Parental LOAEL = 4 mg/kg/day based on clinical 

signs, ophthalmoscopic signs, ulceration of the 

tongue, and cataracts. At HDT, additional findings 

include clinical signs (piloerection, lack of 

grooming, opaque eyes, and ulcers on the palate), 

ophthalmoscopic signs (eye opacity, total cataracts, 

and iritis), and body weight decrements.

Reproductive/Developmental NOAEL = 4 

mg/kg/day.

Reproductive/Developmental LOAEL = 12 

mg/kg/day, based on decreased number of live pups 

per litter on days 1-22, decreased pup body weight 

gain during lactation, and increased incidence of 

kidney lesions.

870.4100a Chronic Toxicity

(rodent) See 870.4300 See 870.4300

870.4100b Chronic Toxicity

(dog)

Technical (26.7% 

diquat cation)

41730301 (1990)

Acceptable/guideline

0, 0.5, 2.5, or 12.5 mg/kg/day

NOAEL = 0.5 mg/kg/day.

LOAEL = 2.5 mg/kg/day based on unilateral 

cataracts in females. At the HDT, bilateral cataracts

and inflammatory lesions in the large intestine.

870.4200a Carcinogenicity (rat) See 870.4300 See 870.4300

870.4200b Carcinogenicity 

(mouse)

Technical (21.09% 

diquat cation)

42219801, 42880701, 

42905901, 42919501 (1991)

Acceptable/guideline

0, 3.56/4.78, 11.96/16.03, or 

37.83/48.27 mg/kg/day (M/F)

NOAEL = 3.56/4.78 mg/kg/day (M/F).

LOAEL = 11.96/16.03 mg/kg/day (M/F) based on 

clinical signs [eye discharge (males), subdued 

behavior (females)], and decreased body 

weight/body weight gain [males]. Diquat was not 

carcinogenic in male or female CD-1 mice.

870.4300 Combined Chronic 

Toxicity/

Carcinogenicity (rat)

Technical (26.5% 

diquat cation)

00145855, 00155474, 

41085601 (1985)

Acceptable/guideline

0, 0.19/0.24, 0.58/0.72, 

2.91/3.64, or 14.88/19.44 

mg/kg/day (M/F)

NOAEL = 0.58/0.72 mg/kg/day (M/F).

LOAEL = 2.91/3.64 mg/kg/day (M/F) based on eye 

lesions [total cataracts]. NOTE: The incidence of 

eye lesions increased with time on study, and effect 

observed at lower dose level with time. Opacity 

first occurred in week 10 at 75 ppm and week 11 at 

375 ppm. There was no treatment-related increase 

in tumor incidence in either sex. 

870.5100 –

870.5915

Mutagenicity 

Toxicity Tests

00061638, 00109564, 

00131383, 00131720, 

00144999, 00148843, 

00148844, 00148845, 

00148847, 00154265, 

40323101 - 40323107 

Negative for mutagenicity in a bacterial gene 

mutation (Ames) assay; however, positive for gene 

mutations in a mammalian cell line (mouse 

lymphoma) but at cytotoxic doses. In addition, 

clastogenic in cultured human lymphocytes, but the 

response was generally weak and observed at 

cytotoxic levels. In contrast, there was no evidence 

of clastogenicity in somatic cells (mouse bone 

marrow) or germinal cells (mouse spermatogonia) 

or unscheduled DNA synthesis (UDS) in rat 

hepatocytes in a series of in vivo studies. Overall, 

the data suggest that there is no concern for 

mutagenicity.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile – Diquat.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification/Doses Results

870.6200a Acute Neurotoxicity 

Screening Battery 

(rat)

Technical (20.1% 

diquat cation)

42666801 (1992)

Acceptable/guideline

0, 25, 75, or 150 mg/kg/day

NOAEL = 75 mg/kg.

LOAEL = 150 mg/kg/day, based on clinical signs 

(piloerection, diarrhea, staining around nose, 

urinary incontinence, upward curvature of the spine, 

tip toe gait, hunched posture, subdued behavior, and 

pinched side)] and decreased body weight gains.

870.6200b Subchronic 

Neurotoxicity 

Screening Battery 

(rat)

Technical (20.8% 

diquat cation)

42616101 (1992)

Acceptable/guideline

0, 1.6/1.9, 8.0/9.5, or 

32.4/38.5 mg/kg/day (M/F)

Systemic Toxicity NOAEL = 8.0/9.5 mg/kg/day

(M/F).

Systemic Toxicity LOAEL = 32.4/38.5 mg/kg/day

(M/F) based on evidence of cataracts and decreased 

body weight gain and food utilization in both sexes. 

870.7485 Metabolism and 

Pharmacokinetics 

(rat)

00065592

Acceptable/guideline when 

considered with other two 

studies

Diquat did not accumulate in tissues and was slowly 

absorbed following either oral or iv exposure to 

single doses of [14C] diquat dibromide to rats or 

mice of both sexes. Following a single dose of 60 

mg/kg, only 5.5% of the radiolabel was excreted in 

urine within 7 days. Following an oral [feeding] 

dose of unlabeled diquat dibromide [250 ppm] to 

rats of both sexes for 2, 4, or 8 weeks, no retention 

of diquat was observed in the brain, liver, lung, 

stomach, small and large intestine, muscle, and 

blood, and little retention in the kidneys [0.18, 0.25, 

and 1.17 ppm during weeks 2, 4, and 8, 

respectively]. Ten minutes after iv injection, there 

were indications that diquat concentrated in 

cartilaginous tissues, liver, and urinary bladder, as 

well as the brain and spinal cord. After 24 hours, 

radiolabel was detected only in the urinary bladder 

and intestines. 

870.7485 Metabolism and 

Pharmacokinetics 

(rat)

00065593

Acceptable/guideline when 

considered with other two 

studies

Rats excreted 6.3% and 89.3% of [14C] in the urine 

and feces, respectively, within 4 days following oral 

exposure, with most being excreted within the first 

48 hours In urine, most of the excreted radioactivity 

was unchanged parent whereas the remaining 1% 

was associated with: diquat monopyridone [0.2%], 

diquat dipyridone [0.1%], and unidentified 

metabolites [0.3%]. In feces, 65.5% of excreted 

[

14C] was detected in sulfuric acid-extractable 

fraction and 15.7% in the ammonium sulfateunextractable fraction. In the sulfuric acid fraction, 

[

14C] was distributed as follows: unchanged diquat 

[57.1%], diquat monopyridone [4.3%], and 

unidentified material [4.1%].

870.7485 Metabolism and 

Pharmacokinetics 

(rat)

00055107

Acceptable/guideline when 

considered with other two 

studies

Following oral dosing, 90% of [14C] was 

eliminated in the feces, indicating that diquat was 

poorly absorbed for the gastrointestinal tract. 

Following a subcutaneous injection of [14C]-diquat 

to circumvent the intestine, nearly all [14C] was 

recovered in the urine within 2 days.

870.7600 In vivo dermal 

penetration

(rat)

41238701 (1989)

Acceptable/guideline

0.05, 0.5, or 5 mg/rat

After 10 hours of exposure, absorption (sum of dose 

measured on/in skin, blood, urine, feces, carcass,

and cage wash) was 5.5%, 5.5%, and 2.5% at 0.05, 

0.5, and 5 mg/rat, respectively.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile – Diquat.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification/Doses Results

870.7800 Immunotoxicity 

(mouse)

48668101 (2011)

Acceptable/guideline

0, 23, 44, or 81 mg/kg/day

Systemic NOAEL = 23 mg/kg/day.

Systemic LOAEL = 44 mg/kg/day based on lower 

body weights and body weight gains.

Immunotoxicity NOAEL = 81 mg/kg/day.

Immunotoxicity LOAEL = not established.
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Appendix B. Calculation of Inhalation Human-Equivalent Concentrations (HECs) and 

Human-Equivalent Doses 

The calculation of HECs accounts for pharmacokinetic (not pharmacodynamic) interspecies 

differences. HECs for residential and occupational scenarios were derived using the POD from 

the route-specific inhalation study and the regional deposited-dose ratio (RDDR). The RDDR 

accounts for the particulate diameter [mass median aerodynamic diameter (MMAD) and 

geometric standard deviation (GSD)] and estimates the different dose fractions deposited along 

the respiratory tract. Table B.1 summarizes the inputs used to obtain the diquat RDDR for HEC 

calculations.

Table B.1. Summary of RDDR Inputs for Diquat.

Study 

MRID

Species 

and 

Strain

Animal 

Body 

Weight 

(g)1

Duration of Exposure

NOAEL 

(mg/L)

LOAEL 

(mg/L)

MMAD 

at 

LOAEL 

(μm)

GSD at 

LOAEL

Respiratory 

Region for 

Effect2

RDDR

hours/day days/week

40301701,

40640801

Fischer 

344 

Rats

152 6 5 0.0001 0.00049 1.9 1.9 PU 0.591

NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. MMAD = mass median aerodynamic diameter. 

GSD = geometric standard deviation. RDDR = regional deposited-dose ratio.

1 Default Fischer 344 rat body weight for combined sexes.

2 ET = extrathoracic, TB = tracheobronchial, PU = pulmonary, TH = thoracic, TR = total respiratory tract, ER = extrarespiratory (systemic). 

The POD from the route-specific inhalation study was adjusted for expected human exposure 

duration. Duration adjustment is performed based on Haber’s law, which assumes that a 

toxicological effect is proportional to the product of exposure level and duration. Animal-tohuman ratios of daily (hours/day) and weekly (days/week) exposures are applied to the animal 

inhalation study POD to result in a duration-adjusted animal POD for HEC conversion. For 

example, expected human exposure for occupational exposures is 8 hours/day and 5 days/week. 

Therefore, the adjusted NOAEL is 7.5x10-5 mg/L.

NOAELadjusted =

0.0001 mg

L

×

6 hr/day

8 hr/day ×

5 days/week

5 days/week =

7.5x10−5 mg

L

For residential handler and outdoor post-application exposures, no duration adjustment was 

applied. For residential indoor post-application exposures, a duration adjustment to 7 days/week 

was applied with no daily exposure adjustment resulting in a duration-adjusted POD of 7.5x10-5

mg/L. For residential bystander exposures, duration adjustments to 24 hours/day and 7 

days/week were applied resulting in a duration-adjusted POD of 1.8x10

-5 mg/L. 

The RDDR was applied to the duration-adjusted POD (except residential handler and outdoor 

post-application exposures with no duration adjustment where the RDDR is applied directly to 

the POD) to calculate HECs. Human-equivalent doses were subsequently calculated from the 

HECs for residential and occupational handler scenarios. The following equation describes the 

conversion from HECs to human-equivalent doses:
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The conversion to human-equivalent doses is an approximation involving the application of a 

conversion factor (CF) that takes into account the typical human volume respired per unit time. 

As the default breathing rate in the HEC calculation is 13.8 L/min for a typical human (body 

weight of 70 kg) under light activity conditions, the corresponding CF is 11.8 L/hr-kg. 

Absorption differences through the respiratory tract as compared to the oral route are expressed 

in the ratio “A.” In current practice, HED customarily assumes “A” to be unity (i.e., the entire 

animal orally administered dose is assumed to be absorbed via the inhalation route). Because the 

inhaled dose depends on activity level which directly impacts breathing parameters (at least until 

blood steady state levels are reached), the activity factor (AF) is a relative ratio that attempts to 

account for differences in respiratory rate due to activity level. Table B.2 lists the different 

exposure scenarios, the corresponding breathing rates associated with these activities, and the AF 

values that should be used for different occupational handler scenarios being assessed. Also 

listed in Table B.2 is the AF value assigned to residential handlers, which is assumed to be equal 

to occupational handlers in non-agricultural settings. The daily exposure duration (D) is 

equivalent to the “hours/day” value used in POD duration adjustment calculations. A summary 

of duration adjustments, HECs, and human-equivalent doses for all potential occupational and 

residential scenarios is presented in Table B.3. 

1 AF = Exposure scenario-specific human breathing rate (L/min) ÷ 13.8 L/min (the rate assumed in HEC calculation). Body 

weight is assumed to be 70 kg for all calculations.

Table B.2. Assigned Activity Factor (AF) Values Based on Different Handler Exposure Scenarios.

Exposure Scenario Human Breathing Rate

(L/min)

HED Calculation Inputs

AF1

Occupational

Pilots, tractor drivers 

(groundboom, airblast) 8.3 0.6

Mixer/loaders, lawn care 

operators (non-agriculture) 16.7 1.2

Handheld spray applications 

(e.g., backpacks, handgun, etc.) 29 2.1

Residential Handlers 16.7 1.2

Human-Equivalent Dose ≈ HEC (mg/L) × CF (L/hr-kg BW) × A × AF × D (hr/day)

HED = Human-Equivalent Dose (mg/kg BW/day).

HEC = Human-Equivalent Concentration (mg/L).

CF = Human-specific value that accounts for volume respired per unit time. CF equals 11.8 L/hr-kg based on the 

default-breathing rate assumed for a typical human (body weight of 70 kg) in the HEC calculation.

A = Absorption ratio through the respiratory tract as compared to the oral route – assumed to be unity. 

AF = Relative ratio that accounts for relative changes in respiratory rate due to activity level. Different AF values 

should be used for different occupational and residential scenarios.

D = Duration of daily exposure in hours: 8 hours assumed for occupational exposures; 24 hours assumed for 

bystanders/residential exposure; and 2 hours is often assumed for residential handler exposures.
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Table B.3. Summary of Inhalation Calculations for Human-Equivalent Concentrations and Doses for Diquat.

Population Scenario

Toxicity Duration 

Adjustment

Human-Equivalent

Concentration

Human-Equivalent Dose

(mg/kg/day; breathing rate specific)

hours/day days/week mg/L mg/m3 8.3 L/min 16.7 L/min 29 L/min

Occupational Handler 8 5 4.43x10-5 0.044 0.0025 0.0051 0.0088

Residential

Handler NA NA 5.91x10-5 0.059 NA 0.0017 NA

Outdoor postapplication NA NA 5.91x10-5 0.059 NA NA NA

Indoor postapplication NA 7 4.22x10-5 0.042 NA

Bystander 24 7 1.06x10-5 0.011 NA

NA = not applicable (the expected duration of the exposure scenario is less than the duration of available inhalation toxicity 

studies; downward adjustments are not permitted).
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Appendix C. Tolerance Summary for Diquat

Table C.1. Tolerance Summary for Diquat (40 CFR §180.226).

Commodity

Established 

Tolerance 

(ppm)

HEDRecommended 

Tolerance (ppm)

Comments

(correct commodity definition)

(a) General. (1) Tolerances are established for residues of the herbicide diquat, including its metabolites and degradates, 

derived from application of the dibromide salt in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring only diquat (6,7-dihydrodipyrido[1,2-a:2′,1′-c]pyrazinediium).

Alfalfa, seed 3.0 3.0

Banana1 0.05 0.02 Move from §180.226(a)(3), harmonize with Codex

Canola, meal 6.0 6.0

Canola, seed 2.0 2.0

Cattle, fat 0.05 0.05

Cattle, meat 0.05 0.05

Cattle, meat byproducts 0.05 0.05

Coffee, bean, green1 0.05 0.02 Move from §180.226(a)(3), harmonize with Codex

Coffee, green bean1

Clover, seed -- 2.0 Recommended in 2002 TRED

Egg 0.05 0.05

Goat, fat 0.05 0.05

Goat, meat 0.05 0.05

Goat, meat byproducts 0.05 0.05

Hog, fat 0.05 0.05

Hog, meat 0.05 0.05

Hog, meat byproducts 0.05 0.05

Horse, fat 0.05 0.05

Horse, meat 0.05 0.05

Horse, meat byproducts 0.05 0.05

Milk 0.02 0.02

Potato 0.1 0.10 Correct number of significant figures to be 

consistent with HED policy

Potato, granules/flakes 0.5 0.50 Move from §180.226(a)(4) and correct number of 

Potato, chips 0.5 0.50 significant figures to be consistent with HED policy

Poultry, fat 0.05 0.05

Poultry, meat 0.05 0.05

Poultry, meat byproducts 0.05 0.05

Sheep, fat 0.05 0.05

Sheep, meat 0.05 0.05

Sheep, meat byproducts 0.05 0.05

(2)(i) Tolerances are established for residues of the herbicide diquat, including its metabolites and degradates, derived 

from application of the dibromide salt to ponds, lakes, reservoirs, marshes, drainage ditches, canals, streams, and rivers 

which are slow-moving or quiescent in programs of the Corp of Engineers or other Federal or State public agencies and to 

ponds, lakes and drainage ditches only where there is little or no outflow of water and which are totally under the control 

of the user, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be 

determined by measuring only diquat (6,7-dihydrodipyrido[1,2-a:2′,1′-c]pyrazinediium).

Animal feed, nongrass, group 18, 

forage

- 0.20

Translated from irrigated grass data Animal feed, nongrass, group 18, 

hay

- 0.20
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Table C.1. Tolerance Summary for Diquat (40 CFR §180.226).

Commodity

Established 

Tolerance 

(ppm)

HEDRecommended 

Tolerance (ppm)

Comments

(correct commodity definition)

Avocado 0.2 0.20 Correct number of significant figures to be 

consistent with HED policy

Berry group 13 0.05 0.05 Berry and small fruit, group 13-07

Cotton, undelinted seed 0.2 0.20 Oilseeds, group 20

Cranberry 0.05 - Member of berry and small fruit, group 13-07; 

individual tolerance not needed.

Fish 2.0 2.0

Fruit, citrus, group 10 0.05 0.05 Fruit, citrus, group 10-10

Fruit, pome, group 11 0.02 0.02 Fruit, pome, group 11-10

Fruit, stone, group 12 0.02 0.02 Fruit, stone, group 12-12

Grain, cereal, forage, fodder and 

straw, group 16

0.02 0.02

Grain, cereal, group 15 0.02 0.02

Grape 0.05 - Member of berry and small fruit, group 13-07; 

individual tolerance not needed.

Grass, forage, fodder and hay, 

group 17

0.2 0.20 Correct number of significant figures to be 

consistent with HED policy

Herb and spice, group 19 - 0.20 Translated from irrigated grass data

Hop, dried cones 0.2 0.20 Correct number of significant figures to be 

consistent with HED policy

Nut, tree, group 14 0.02 0.02 Nut, tree, group 14-12

Shellfish 20.0 20 Correct number of significant figures to be 

consistent with HED policy

Strawberry 0.05 - Member of berry and small fruit, group 13-07; 

individual tolerance not needed.

Sugarcane, cane 0.2 0.20 Correct number of significant figures to be 

consistent with HED policy

Vegetable, brassica, leafy, group 

5

0.05 0.05 Vegetable, Brassica, leafy, group 5

Vegetable, bulb, group 3 - 0.02 Translated from irrigated carrot data

Vegetable, cucurbit, group 9 0.02 0.02

Vegetable, foliage of legume, 

group 7

0.2 0.20 Correct number of significant figures to be 

consistent with HED policy

Vegetable, fruiting, group 8 0.05 0.05 Vegetable, fruiting, group 8-10

Vegetable, leafy, except brassica, 

group 4

0.05 0.05 Vegetable, leafy, except Brassica, group 4

Vegetable, leaves of root and 

tuber, group 2

- 0.02 Translated from irrigated carrot data

Vegetable, root and tuber, group 1 0.02 0.02 Vegetable, root and tuber, group 1, except potato

Vegetable, seed and pod 0.05 0.05 Vegetable, legume, group 6

(3) Tolerances are established for residues of the herbicide diquat, including its metabolites and degradates, derived from 

application of the dibromide salt in or on the commodities in the table below. Compliance with the tolerance levels 

specified below is to be determined by measuring only diquat (6,7-dihydrodipyrido[1,2-a:2′,1′-c]pyrazinediium).

Soybean, hulls 0.6 - Not required as use on soybeans cancelled

1

 There are no U.S. registrations as of May 26, 2010.
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Appendix D. Physical/Chemical Properties

Table D.1. Physicochemical Properties of Diquat.

Parameter Value Reference

Molecular Weight 344.1 (Cation – 184) The Pesticide Manual 11th

Edition

Melting point/range 300 °C D277710

pH Not Provided NA

Density (20°C) 1.22-1.27 g/cm3 The Pesticide Manual 11th

Edition

Water solubility (20°C) 700 g/L D277710

Solvent solubility slightly soluble in alcohol and 

hydroxylic solvents, and practically 

insoluble in nonpolar organic solvents

D277710

Vapor pressure at 25°C <1×10-8 mm Hg Vencill, W.K. 2002. 

Herbicide Handbook, 8th

Edition

Dissociation constant (pKa) Not Provided NA

KOW Octanol/water partition coefficient as 

Log POW at 20°C

-4.60 The Pesticide Manual 11th

Edition

UV/visible absorption spectrum Neutral and acidic conditions - one 

major peak at 309.5 nanometers. 

Basic conditions - two major peaks at 

309.0 and 217.0 nanometers.

D349998
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Appendix E. Summary of Registered Uses of Diquat 

Table E.1. Summary of Directions for Use of Diquat.

Applic. 

Timing, 

Type, and 

Equip.

Crop

Formln. 

[EPA Reg. 

No.]

Applic. 

Rate1

Max. No. 

Appl. Per 

Season

Max. 

Seasonal 

Appl. Rate2

PHI

(Days)

Use Directions 

and Limitations8

Use Site 1 (Terrestrial Crop and Farmland)

Pre-harvest/

desiccation 

Ground and

Aerial

Alfalfa, Clover,

(Seed crop) SC

(EPA Reg.# 

100-1061)

0.5 

lb ai/Acre

2

1.0 lb 

ai/Acre

3 Do not apply 

through 

irrigation 

systems.

Do not graze or 

feed treated 

forage to 

livestock.

Do not use seed 

from treated 

plants for food, 

feed, or oil 

purposes.

24C:

FL- 000009

SC-000005

Potato, Canola 7

Non-bearing 

crops:

Ground 

Directed 

Spray

Crop Groups 3:

4, 13-07, 14-12, 10-10, 

99, 12-12, 11-10

SC

(EPA Reg.# 

100-1061)

5

2.5 lb 

ai/Acre 365

Post-Harvest 

burn down:

Groundboom.

Tomato Vines 0.38 lb 

ai/Acre

2

0.75 lb 

ai/Acre

N/A

Cantaloupe Vines

SC

(EPA Reg.# 

100-1061)

0.25 lb 

ai/Acre

0.5 lb 

ai/Acre

Cucumber, Squash, 

Watermelon

0.38 lb 

ai/Acre

0.75 lb 

ai/Acre

Acorn squash, Peppers 0.5 lb 

ai/Acre 1 lb ai/Acre

Weed 

control:

Middle Rows

Grounddirected 

Spray

Eggplant, Green 

Pepper, Tomato

SC

(EPA Reg.# 

100-1061)

0.5 lb ai/A

2 1 lb ai/Acre 30

Do not apply 

when wind 

speed exceeds 5 

mph.

24C:

FL-000010

PR-030001

Pre-Harvest 

desiccation

Ground and 

Aerial

Carrots, Coriander, 

Radishes, Spinach, 

Sugar Beets, Table 

Beet, Turnips, 

Calendulas

SC

(EPA Reg.# 

100-1061)

1

0.5 lb 

ai/Acre 3

Do not apply 

through 

irrigation 

systems. Use 

only on nonedible oilseed 

varieties of 

calendula. 

24C:

WA-040011

OR-080025

ID-100006

MN-090006

Non-Crop or 

Non-Planted 

Areas on 

Farms

Grounddirected

Fence Lines, 

Farmyards, Farm 

Buildings, Fuel 

Storage Areas, barrier 

Strips, and Equipment 

Areas around ponds, 

lakes and drainage 

ditches on farms.

SC

(EPA Reg.# 

100-1061)

0.5 lb 

ai/Acre 10 5 lb ai/Acre N/A

For spot 

treatments, apply 

2 qt product/100 

gallon water (or 

22 ml product/1 

gallon water).

Use Site 2 (Non-Crop Terrestrial)

Pre-harvest 

Desiccation

Grounddirected

Ornamental seed crops

SC

(EPA Reg.#

100-1091, 

100-1390)

0.5 lb 

ai/Acre 3

1.5 lb 

ai/Acre N/A

Do not apply 

through any type 

of irrigation 

system. For 

seed crop only. 

Not for food or 

Commercial 

Greenhouse (beneath 

benches), field grown 

and container stock 

and other similar areas 
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Table E.1. Summary of Directions for Use of Diquat.

Applic. 

Timing, 

Type, and 

Equip.

Crop

Formln. 

[EPA Reg. 

No.]

Applic. 

Rate1

Max. No. 

Appl. Per 

Season

Max. 

Seasonal 

Appl. Rate2

PHI

(Days)

Use Directions 

and Limitations8

Landscape, Industrial, 

Commercial areas4

including golf courses

fiber crops. Not 

allowed in 

California.

Turf Renovation

2 1 lb ai/Acre Dormant Established 

Turf Grass

Pre-plant, 

Preemergence, 

PostEmergence 

Directed 

Spray

(Spot 

Treatment)

Commercial 

Greenhouse (beneath 

benches), field grown 

and container stock 

and other similar areas 0.01 lb 

ai/gal 5 2 lb ai/Acre

Not for food or 

fiber crops. 

Avoid spray 

contact with 

foliage of food 

crops or 

ornamental 

plants or other 

desirable 

vegetation.

Landscape, Industrial, 

Commercial, 

Residential and Public 

Areas 

Use Site 3 (Aquatic - Occupational and Residential)

Aquatic 

Broadcast 

around lakes, 

ponds, 

drainage 

ditches, 

reservoirs, 

marshes, 

canals and 

rivers

Floating and Marginal 

Weeds

SC

(EPA Reg.#

100-1091, 

100-1390)

4 lb ai/. 

Acre/4 feet 

10

See table 4.1.A 

in appendix for 

extensive 

directions and 

limitations.

24C

FL-030006

FL-110009

ID-070012

AL-07001

GA-080004

NY-030001

NY-120007

Submersed Weeds

Standing and Flowing 

Water - Submerged 

Weeds

Still Water -

Submerged Weeds

Still Water - Floating 

Weeds

1.5 lb ai/. 

Acre-ft

Still Water -

Duckweed, Cattails

2 lb ai/. 

Acre-ft

Aquatic5

Spot 

Treatment

Floating and Marginal 

Weeds

SC

(EPA Reg.#

100-1091, 

100-1390)

0.04 lb 

ai/gal

40 lb/Sq. 

Acre

N/A

See Table 4.1.A 

in Appendix of 

the most recent 

ORE memo. 0.000092 lb 

ai ft2 N/A

Use Site 3 (Residential)6

Manually 

Pressurized 

Handwand

Gardens/Trees/Turf

SC

(EPA Reg.#

100-1091, 

100-1390)

0.01 lb 

ai/gal

N/A N/A N/A N/A

0.5 lb 

ai/Acre

Backpack 

Sprayer

0.01 lb 

ai/gal

Trigger-spray 

Bottle

0.0025 lb 

ai/bottle7

1, 2 Application rates primarily based on use information provided by registrant (supplied by email from PRD 9/5/2014). The use 

information provided was noted to be based primarily on representative Section 3 and 24C labels from Syngenta Crop 

Protection. In addition, information provided in the TRED (D281890) for diquat was used for the residential use information.

3. Crop groups (4, 13-07, 14-12, 10-10, 99, 12-12, 11-10): vegetable, leafy, except Brassica; fruit, berry and small fruit; nut, tree;

fruit, citrus; fruit, stone; fruit, pome.

4. Areas of use; around trees ornamental gardens, beneath commercial greenhouse benches. Other non-crop areas: buildings, 

parking lots, cart paths, patios, dividers, pipelines, driveways, public utility lines, electric utilities, pumping stations, fence 

lines, railroad beds/yards, golf courses, rights of way, highways, roads, landscape beds, roadsides, lawns, transformer stations 

and substations, medians, walkways, non-flooded portions of ponds, lakes and ditches.

5. Label rate: 4 lb ai/Acre x Acre/43,560 sq ft = 0.000092 lb ai/ft sq.

6. Residential use information: See TRED (D281890) for specifics.
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7. TRED - (D281890): Trigger Sprayer: high-end = 0.01 lb ai.gal, so: 0.01 lbs ai/gal x gal/128 fl. oz. x 32 fl. oz/bottle = 0.0025 

lb ai/bottle (32 fl. oz).

8. REI = 24 hr. (for occupational uses).
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Appendix F. International Residue Limits

Diquat (032201; 4/15/2015)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

§180.226

(a) General. (1) Tolerances are 

established for residues of the herbicide 

diquat, including its metabolites and 

degradates, derived from application of 

the dibromide salt in or on the 

commodities in the table below. 

Compliance with the tolerance levels 

specified below is to be determined by 

measuring only diquat (6,7-

dihydrodipyrido[1,2-a:2′,1′-

c]pyrazinediium).

6,7-dihydrodipyrido[1,2-

a:2',1'-c]pyrazinediium 

Diquat

The residue is not 

fat soluble.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico1 Codex

Alfalfa, seed 3.0

Banana 0.02 0.02 (*) 

Cattle, fat 0.05

Cattle, meat 0.05 0.05 meat 0.01 (*) meat 

from mammals 

other than marine 

mammals) 

(proposed)

Cattle, meat byproducts 0.05 0.05 meat byproducts 0.01 (*) edible 

offal 

(mammalian) 

(proposed)

Canola, meal 6.0

Canola, seed 2.0 1 1.5

Coffee, green bean 0.02 0.02 (*)

Egg 0.05 0.05 0.01 (*) 

(proposed)

Goat, fat 0.05

Goat, meat 0.05 0.05 meat 0.01 (*) meat 

from mammals 

other than marine 

mammals) 

(proposed)

Goat, meat byproducts 0.05 0.05 meat byproducts 0.01 (*) edible 

offal 

(mammalian) 

(proposed)

Hog, fat 0.05

Hog, meat 0.05 0.05 meat 0.01 (*) meat 

from mammals 

other than marine 

mammals) 

(proposed)

Hog, meat byproducts 0.05 0.05 meat byproducts 0.01 (*) edible 

offal 

(mammalian) 

(proposed)
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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Horse, fat 0.05

Horse, meat 0.05 0.05 meat 0.01 (*) meat 

from mammals

other than marine 

mammals) 

(proposed)

Horse, meat byproducts 0.05 0.05 meat byproducts 0.01 (*) edible 

offal 

(mammalian) 

(proposed)

Milk 0.02 0.05 0.001 (*) 

(proposed)

Potato 0.10 0.1 0.1

Potato, granules/flakes 0.50

Potato, chips 0.50

Poultry, fat 0.05

Poultry, meat 0.05 0.05 0.01 (*) 

(proposed)

Poultry, meat byproducts 0.05 0.05 0.01 (*) poultry 

edible offal of 

(proposed)

Sheep, fat 0.05

Sheep, meat 0.05 0.05 meat 0.01 (*) meat 

from mammals 

other than marine 

mammals) 

(proposed)

Sheep, meat byproducts 0.05 0.05 meat byproducts 0.01 (*) edible 

offal 

(mammalian) 

(proposed)

US Canada Codex

(2)(i) Tolerances are established for 

residues of the herbicide diquat, 

including its metabolites and degradates, 

derived from application of the 

dibromide salt to ponds, lakes, 

reservoirs, marshes, drainage ditches, 

canals, streams, and rivers which are 

slow-moving or quiescent in programs 

of the Corp of Engineers or other 

Federal or State public agencies and to 

ponds, lakes and drainage ditches only 

where there is little or no outflow of 

water and which are totally under the 

control of the user, in or on the 

commodities in the table below. 

Compliance with the tolerance levels 

specified below is to be determined by 

measuring only diquat (6,7-

dihydrodipyrido[1,2-a:2′,1′-

c]pyrazinediium).

6,7-dihydrodipyrido[1,2-

a:2',1'-c]pyrazinediium 

Diquat

The residue is not 

fat soluble.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US

Avocado 0.20
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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Animal feed, nongrass, 

group 18, forage

0.20

Animal feed, nongrass, 

group 18, hay

0.20

Berry and small fruit, 

group 13-07

0.05 0.02 grapes 0.05 strawberry

Oilseeds, group 20 0.20 0.05 sunflower seed

0.5 flaxseeds

1 mustard seeds

0.5 Solin

0.9 sunflower 

seed

Fish 2.0

Fruit, citrus, group 10-10 0.05 0.02 (*)

Fruit, pome, group 11-10 0.02 0.02 apples, Asian pears, 

crabapples, loquats, 

mayhaws, pears, quinces, 

0.02 (*)

Fruit, stone, group 12-12 0.02 0.02 apricots, fresh prune 

plums, nectarines, peaches, 

plumcots, plums, sweet 

cherries, tart cherries 

0.02 (*)

Grain, cereal, forage, 

fodder and straw, group 16

0.02

Grain, cereal, group 15 0.02 0.02 barley, field corn, oats, 

rye, sweet corn kernels plus 

cob with husks removed, 

triticale, wheat

5 barley

2

3 oats, wheat, 

wheat bran, 

unprocessed, 

wheat wholemeal 

(proposed)

0.53 wheat flour 

(proposed)

Grass, forage, fodder and 

hay, group 17

0.20

Herb and spice, group 19 0.20

Hop, dried cones 0.20

Nut, tree, group 14-12 0.02 0.02 (*) cashew 

nut

Shellfish 20

Sugarcane, cane 0.20

Vegetable, Brassica, leafy, 

group 5

0.05 0.02 bok choy Chinese 

cabbages, broccoli, broccoli 

raab, Brussels sprouts, 

cabbages, cauliflower, 

Chinese broccoli, Chinese

mustard cabbages, collards, 

kale, kohlrabi, mustard 

greens, mustard spinach, 

Napa Chinese cabbages, 

rape leaves

Vegetable, bulb, group 3 0.02 0.02 dry bulb onions

0.02 green onions

Vegetable, cucurbit, group 

9

0.02 0.02 cucumbers

Vegetable, foliage of 

legume, group 7

0.20 50 pea hay or pea 

fodder (dry)
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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico1 Codex

Vegetable, fruiting, group 

8-10

0.05 0.01 (*) fruiting 

vegetables other 

than cucurbits 

(except sweet 

corn fungi and 

mushrooms)

Vegetable, leafy, except 

Brassica, group 4

0.05

Vegetable, leaves of root 

and tuber, group 2

0.02

Vegetable, root and tuber, 

group 1, except potato

0.02 0.02 carrot roots, garden 

beet roots, turnip roots

Vegetable, legume, group 

6

0.05 0.2 Dry (adzuki beans, 

beans, black-eyed peas, 

broad beans, catjang seeds, 

chickpeas, field peas, guar 

seeds, kidney beans, lablab 

beans, lentils, lima beans, 

moth beans, mung beans, 

navy beans, pigeon peas, 

pink beans, pinto beans, rice 

beans, southern peas, tepary 

beans, urd beans); grain 

lupin

0.05 dry soybeans

0.05 beans (dry) 

(proposed)

0.23lentil (dry) 

(proposed)

0.3 peas, soya 

bean (all dry)

MRLs with NO US Equivalent

Cajou (pseudofruit) 0.02 (*)

Cashew apple 0.02 (*)

Completed: M. Negussie; 04/29/15

1 Mexico adopts U.S. tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

3 = MRLs are under the 4 year rule awaiting data.
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Appendix G. Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the Pesticide Handlers Exposure Database (PHED) 1.1, the Agricultural Handler Exposure Task 

Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) database

and the Agricultural Reentry Task Force (ARTF) database are (1) subject to ethics review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

ethics requirements. For certain studies, the ethics review may have included review by the 

Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, 

can be found at the Agency website11. 

 

11 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html