UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES

March 25, 2002

MEMORANDUM

SUBJECT: Diquat Dibromide HED Risk Assessment for Tolerance Reassessment Eligibility

Document (TRED.) PC Code No: 032201; DP Barcode: D281890; Submission 

Barcode: S611057

FROM: Becky Daiss, Environmental Health Scientist

Reregistration Branch 4

Health Effects Division (7509C)

THROUGH: Susan V. Hummel, Branch Senior Scientist

Reregistration Branch 4

Health Effects Division (7509C)

TO: Tyler Lane, Chemical Review Manager

Betty Shackleford, Branch Chief

Registration Branch

Special Review and Reregistration Division (7508C)

Attached is the Health Effects Division (HED’s) revised risk assessment conducted to 

support a Tolerance Reassessment Eligibility Decision (TRED) for diquat dibromide. This 

document updates the March 6, 2001 version by incorporating revisions to the drinking water 

exposure assessment provided by the Environmental Fate and Effects Division (EFED). The 

disciplinary science chapters and other supporting documents are included as appendices as 

follows:

Use Closure Memo. Tyler Lane (10/31/01)

Report of the Hazard Identification Assessment Review Committee. Linda Taylor ( 12/14/01, HED DOC NO 014670)

Report of the FQPA Safety Factor Committee. C. Christiansen (11/27/10, TXR NO. 0050293 )

Report of the Metabolism Assessment Review Committee. T. Morton (9/13/01, D277764)

Product & Residue Chemistry Chapter. T. Morton (12/12/01, D277710)

Residential Exposure Assessment. T. Brennan (12/14/01, D279507)

Dietary Exposure and Risk Estimates for Tolerance Reassessment. B. Daiss (12/11/01, D277766)

Incident Report. M. Spann and J. Blondell, Ph.D (10/15/01, D278482)

Tier I Drinking Water and Aquatic Ecological Exposure Assessments for Diquat Dibromide. J Breithaupt (3/5/02, D281199)

Toxicology Chapter, Linda Taylor (12/14/01, D279696)

Table of Contents
 2  44

 pg.

1.0 EXECUTIVE SUMMARY....................................................................................................3

2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION ....................................8

3.0 HAZARD CHARACTERIZATION......................................................................................9

3.1 Hazard Profile ........................................................................................................................9

3.1.1 Acute Toxicity............................................................................................................9

3.1.2 Toxicity Profile ........................................................................................................10

3.1.3 Hazard Characterization...........................................................................................14

3.2 FQPA Considerations ..........................................................................................................14

3.3 Dose Response Assessment .................................................................................................15

3.3.1 Dietary Endpoints.....................................................................................................15

3.3.2 Residential Exposure Endpoints..............................................................................16

3.4 Endocrine Disruptor Effects.................................................................................................18

4.0 EXPOSURE ASSESSMENT ..............................................................................................19

4.1 Summary of Registered Uses...............................................................................................19

4.2 Dietary Exposure/Risk Pathway...........................................................................................20

4.2.1 Residue Profile.........................................................................................................20

4.2.2 Dietary Exposure/Risk Assessment .........................................................................24

4.3 Drinking Water Exposure/Risk Pathway .............................................................................26

4.3.1 Environmental Fate Assessment ..............................................................................26

4.3.2 Estimated Environmental Concentrations................................................................26

4.4 Residential Exposure/Risk Assessment ...............................................................................29

4.4.1 Home Uses...............................................................................................................29

4.4.2 Recreational .............................................................................................................36

4.5 Incident Report Summary ....................................................................................................38

4.5.1 Residential Handler Incidents..................................................................................39

4.5.2 Post-Application and Recreational Incidents...........................................................39

5.0 AGGREGATE RISK ASSESSMENT AND RISK CHARACTERIZATION....................39

5.1 Acute Aggregate Risk Assessment ......................................................................................39

5.2 Short-Term Aggregate Risk Assessment .............................................................................40

5.3 Chronic Aggregate Risk Assessment...................................................................................42

6.0 CUMULATIVE EXPOSURE AND RISK..........................................................................43

7.0 DATA NEEDS.....................................................................................................................43
 3  44

1.0 EXECUTIVE SUMMARY

EPA issued a Reregistration Eligibility Decision (RED) for diquat dibromide in July, 1995. 

The RED recommended revisions to some of the existing tolerances for diquat dibromide. The 

purpose of this document is to reassess the findings and conclusions presented in the RED to 

determine whether infants and children exhibit enhanced sensitivity from dietary and/or residential 

exposure to diquat dibromide. This action is required under the Food Quality Protection Act 

(FQPA) of 1996. Occupational exposure/risk is not considered for this TRED. However, a 

separate but concurrent reassessment of occupational exposure/risk is also being conducted to 

address the registrant’s request to modify diquat dibromide label requirements (T. Brennan, 

D279612).

Use Profile

Diquat dibromide is a non-selective contact herbicide, algicide, dessicant, and defoliant. 

As a herbicide/algicide, it is used to control aquatic and terrestrial weeds. It is used as a preharvest 

dessicant/defoliant to facilitate the harvest of potatoes and various crops grown for seed. Its 

largest use is as a dessicant on potato crops. Other minor food use applications include use as a 

dessicant on crops grown for seed that is used for feed, i.e., alfalfa, sorghum, soybean, and clover. 

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

plants and livestock. Non-food use applications include use as a preharvest dessicant on carrot, 

radish and turnip grown for seed; as a post-harvest dessicant on cantaloupe, cucumber, pepper, 

squash, tomato, and watermelon; and as a dessicant/defoliant for commercial greenhouses and 

nurseries, ornamental seed crops, and commercial and residential landscaping and grounds 

maintenance. Diquat dibromide is rapidly absorbed by green plant tissue and interacts with the 

photosynthesis process. It works as an herbicide/dessicant by reacting with molecular oxygen to 

produce a superoxide anion in treated plants. The oxidative activity, which occurs subsequent to 

formation of the oxygen radicals, rapidly destroys plant cell membranes. Herbicidal activity is 

usually quite rapid with effects visible in a few days.

Diquat dibromide is formulated as a soluble concentrate and ready-to-use liquid. As an 

herbicide/algicide used to control algae and aquatic weeds, it is applied by direct pouring, handheld or mechanical sprayer, and injection below the water surface. As a terrestrial herbicide and 

crop dessicant/defoliant, it is applied by hand-held sprayer, aircraft, or ground equipment. 

Currently, 43 products containing the active ingredient diquat dibromide are registered and 

marketed under the trade name diquat dibromide. The largest markets for diquat, in terms of total 

pounds of active ingredient, include: aquatic uses (40%), potatoes (35%), home & garden (10%), 

and alfalfa for seed (5%). Most of the usage is in FL, ME, ND, NY, WA, and WI (T. Lane, Use 

Closure Memo, 10/31/01).
 4  44

Regulatory History

In July, 1995, EPA issued a RED for diquat dibromide. In the RED, the Agency

recommended changes to published tolerances for several commodities, including fish (increase 

from 0.1 to 2.0 ppm) and fruiting vegetables (increase from 0.02 to 0.05 ppm). The recommended 

changes to the tolerances have not yet been implemented. Based on the risk assessment conducted 

for the RED, EPA concluded that acute and chronic dietary risks from exposure to diquat are 

minimal, but found risks of concern for some worker and residential exposure scenarios. To 

address these risks EPA required the following: closed mixing/loading of diquat dibromide for 

aerial applications; a longer interim restricted entry level (REI) and more stringent personal 

protective equipment (PPE) for uses within the scope of the Worker Protection Standard for 

Agricultural Pesticides; a four-day reentry interval to reduce post-application exposure for workers 

not covered by the worker protection standard (e.g., golf course workers); and a ban on broadcast 

treatments to reduce the potential for post-application residential exposure. Diquat labels have not 

yet been revised in accordance with the requirements outlined in the RED. The RED also 

addressed the occurrence of ethylene dibromide (EDB) which is used as a starting material in the 

manufacture of diquat dibromide and may be present as a process impurity in final formulations. 

EDB is considered a carcinogen and all pesticide uses of EDB have been canceled. Previous EPA 

assessments indicate that the presence of EDB in diquat formulations does not pose a significant 

dietary risk. In addition, the registrant certified an upper limit of 10 ppm EDB in diquat 

dibromide, and demonstrated that EDB does not persist as an impurity in diquat dibromide. 

In January, 1998, HED conducted a human health risk assessment to evaluate the effect of 

a change in application and use patterns on potatoes and a new use on dried shelled peas and beans 

(W Cutchin, 1/23/98, D220714). Results from the 1998 assessment were consistent with the RED, 

as were the recommendations for additional restricted entry and PPE requirements. 

Only manufacturing use products (MPs) are subject to a reregistration eligibility decision. 

There are currently only 2 diquat dibromide MPs; 41.1% and 37.3% a.i. formulation intermediates. 

Both of these MPs are currently registered to Syngenta Crop Protection, Inc. The products were 

transferred from Zeneca to Syngenta and the product chemistry information for the Zeneca MPs 

was a repack of a registered product which is now canceled. From the confidential statements of 

formula provided by Syngenta, it appears that the manufacturing process for the current MPs has 

changed. Therefore, the product chemistry data submitted for the canceled products do not satisfy

the requirements for the Syngenta products and a complete updated product chemistry data 

package on the currently registered technicals must be submitted to support continued registration. 

Hazard Identification and Dose Response Assessment

The toxicology data base is adequate to characterize the toxicity of diquat dibromide, 

Diquat dibromide 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 
 5  44

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

sensitizer, but it is considered a moderate-to-severe eye irritant (Toxicity Category II). 

Subchonic and chronic studies in several species indicate multiple target sites for diquat 

dibromide toxicity. In subchronic dermal exposure studies in rats, diquat dibromide showed 

evidence of severe systemic toxicity, i.e. high mortality and clinical signs. In subchronic 

inhalation study in rats, the lung was determined to be the primary target site for inhalation 

toxicity. Chronic feeding studies in dogs, rats, mice, and rabbits indicate that target sites include 

the eyes and kidneys in both males and females and the adrenals and epididymides in males. 

Developmental toxicity was observed in rat, rabbit, and mouse studies, and reproductive toxicity

was observed in the rat in both generations. Rat and rabbit studies provided evidence of maternal 

toxicity. Acute and subchronic studies in mice and rats provided no evidence of neurotoxicity. 

Available data provide no evidence of endocrine disruption following exposure to diquat 

dibromide. Carcinogenicity studies in rats and mice provided no evidence of an increased tumor 

incidence and diquat dibromide was classified as a Category E (evidence of non-carcinogenicity to 

humans) by the HED Cancer Peer Review Committee based on the 1999 EPA Draft Proposed 

Guidelines for Carcinogen Risk Assessment. The weight of the evidence was predominantly

negative for mutagenicity. The data provided no indication of increased sensitivity of rats, mice, or 

rabbits to in utero and/or early postnatal exposure to diquat dibromide. HED’s FQPA committee 

determined that the FQPA safety factor could be removed (1x) in assessing the risk posed by this 

chemical because the toxicological database is complete for FQPA assessment, there is no 

indication of quantitative or qualitative increased susceptibility of rats or rabbits to in utero and/or 

postnatal exposure, a developmental neurotoxicity study is not required, and the dietary (food and 

drinking water) and residential exposure assessments will not underestimate potential exposures 

for infants and children. There are no toxicological study data gaps at this time. 

Risk assessments were conducted for the exposure scenarios listed below. Route-specific 

endpoints were selected for all but the dermal scenario. The dermal exposure endpoint is based on 

oral toxicity studies and therefore requires application of a dermal absorption factor (4.1%).

– acute dietary(general population): NOAEL= 75 mg/kg/day RfD=0.75 mg/kg/day

– chronic dietary: NOAEL= 0.5 RfD = 0.005 mg/kg/day

– short-term oral: NOAEL= 1 mg/kg/day MOE=100 

– short-term dermal: NOAEL= 1 mg/kg/day MOE=100 

Exposure Assessment

Analysis of dietary, drinking water, and residential exposure pathways were included in 

the risk assessment for the diquat TRED. Sources of dietary exposure include potatoes and 

various crops grown for seed that is used for feed (e.g. alfalfa, sorghum) to which diquat has been 

applied as a dessicant. Residues in plants and livestock feeds may also occur through irrigation of 

crops with water containing diquat residues, resulting in dietary exposure through consumption of 

crops and secondary residues in livestock tissues. Drinking water exposure may occur due to run-
 6  44

off from terrestrial use of diquat and use of diquat in lakes, ponds, streams, etc., to control aquatic 

weeds. Residential application and post-application exposure may occur through the use of diquat 

on turf grass and weeds. Potential residential exposure routes include inhalation and dermal 

exposure to adult applicators/handlers, postapplication dermal exposure to adults and children, and 

incidental ingestion of residue by toddlers via hand-to-mouth activity and ingestion of grass or soil 

from a treated area.

Risk Assessment and Risk Characterization

Risk assessments were conducted for dietary, drinking water, and residential exposure 

pathways. An aggregate assessment of risk from the combined food, drinking water and 

residential pathways was also conducted. A cumulative risk assessment considering risks from 

other pesticides or chemical compounds having a common mechanism of toxicity has not been 

conducted for this TRED because HED has not yet determined if there are any other chemical 

substances that have a mechanism of toxicity common with that of diquat dibromide. 

Food Pathway Exposure and Risk

HED conducted acute and chronic dietary exposure analysis using the Dietary Exposure 

Evaluation Model (DEEM). The acute and chronic dietary exposure/risk analyses were 

conducted using a conservative deterministic (Tier I) methodology. The Tier I analysis assumes 

that; 1) residues are present at published tolerances for registered uses and at recommended 

tolerances for proposed new uses, and 2) 100% crop treated (CT) for all commodities with existing 

and/or recommended tolerances. Tier I acute and chronic dietary analyses were conducted for the 

general U.S. population and all population subgroups. 

The acute and chronic dietary risks are expressed as a percentage of the acute or chronic 

Population Adjusted Dose (aPAD or cPAD). A dietary risk of 100% of the PAD is the target level 

of exposure that should not be exceeded, (i.e., the estimated risk that is less than 100% of PAD is 

not of concern). The Population Adjusted Dose (PAD) is the Acute reference dose (RfD) or the 

Chronic RfD modified by the FQPA Safety Factor. In the acute dietary assessment for diquat, 

acute exposure (mg/kg/day) was compared to the aPAD which is based on the acute RfD and a 

FQPA safety factor of 1x.. For the chronic dietary assessment, chronic exposure was compared to 

the cPAD which is based on the chronic RfD and an FQPA factor of 1x. Based on these analyses, 

acute and chronic dietary risk associated with exposure to diquat from existing and proposed uses 

are below the Agency’s level of concern for the general US population and population subgroups. 

The 95th percentile acute exposure estimates were < 100% of the aPAD. The highest acute 

exposures ( 0.0054 mg/kg/day) were in Children 1-6 years old (<1% aPAD). The chronic 

exposure estimates were <100% of the cPAD, with the highest chronic exposure (0.0031 

mg/kg/day) occurring in children 1-6 years old (62% cPAD).
 7  44

Residential Pathway Exposure and Risk

Potential residential scenarios include exposures to handlers (mixers, loaders, applicators, 

etc.) that occur during handling and application of diquat and/or to persons entering treated sites 

after its application. This TRED estimates exposure and risk for four residential handler scenarios 

four post-application scenarios, and two recreational scenarios. Residential handler scenarios 

include: 1) mixing, loading, and applying with a low pressure handwand (for lawns and backyard 

ponds), 2) mixing, loading, applying with a backpack sprayer(for lawns and backyard ponds), 3) 

applying with an aerosol sprayer (for lawns), and 4) applying with a trigger pump sprayer. 

Postapplication scenarios include: 1) dermal exposure to treated turf grass (adults and children); 2) 

toddler ingestion of treated turf grass via object-to-mouth activities; 3) toddler ingestion of residue 

via hand-to-mouth activity while on treated turf grass; and 4) toddler ingestion of soil from treated 

areas. Recreational exposures include: 1) golfer exposure from playing on treated turf grass; and 

2) exposure from swimming in treated lakes and ponds. A target Margin of Exposure (MOE) of 

100 is considered adequate for all residential exposure routes. With one exception, the MOEs 

estimated for all of the residential exposure scenarios described above showed no risks of concern 

(i.e. all MOEs were 100 or greater). An assessment of aggregate residential risks to children 1-6 

years from post-application exposure to broadcast treated lawns resulted in an estimated MOE of 

70, which exceeds the Agency’s level of concern. The residential aggregate risk combines 

screening level risk estimates from individual exposure pathways and should be viewed as a highly

conservative estimate which is certain to over-estimate risk. A refined analysis would result in 

lower exposure estimates and higher MOEs.

Drinking Water Pathway Exposure and Risk

The Environmental Fate and Effects Division (EFED) performed a Tier I drinking water 

assessment for diquat dibromide for both terrestrial and aquatic uses. EFED used both computer 

models and monitoring data to estimate environmental concentrations of diquat in surface and 

ground water. For terrestrial uses, EFED assessed preharvest application to potatoes, alfalfa, and 

clover with aerial and ground equipment and application to clover trees, vines, small fruits, and 

vegetables using directed spray from ground equipment. The FQPA Index Reservoir Screening 

Tool (FIRST) model was used to estimate environmental concentrations in drinking water from 

surface water contaminated by terrestrial use of diquat. The surface water estimated 

environmental concentrations (EECs) generated by FIRST ranged from 6.3- 13.2 ug/L (ppb) for 

peak exposure and 0.2-0.4 ug/L for average annual exposure. 

EFED relied on monitoring data to estimate concentrations in groundwater contaminated 

by terrestrial uses. Based on municipal monitoring data, EFED recommends use of EPA’s Office 

of Waters (OW) maximum contaminant level (MCL) of 20 ppb for both peak and average annual 

EECs for groundwater concentrations due to terrestrial use of diquat. EFED also used monitoring 

data to estimate surface water and ground water concentrations from aquatic uses of diquat. For 

surface water, EFED recommends use of the MCL of 20 ppb for both acute (peak) and chronic 

(annual average) EECs. For the aquatic use EFED relied on use information from the U.S. Corp of 
 8  44

Engineers and the states of Florida, Minnesota, and Michigan. The assessed aquatic uses include 

application to lakes and flowing streams. EFED also recommends use of the MCL of 20 ppb for 

both acute and chronic EECs for groundwater. EFED recommends use of the same EECs for both 

surface and groundwater contaminated by aquatic uses of diquat because diquat is used near wells 

located next to lakes and ponds resulting in interaction between surface and ground water. 

Aggregate Exposures and Risks

The aggregate risk assessment combines the exposure assessments conducted for dietary, 

drinking water, and residential exposure. Since there is potential for concurrent exposure via the 

food, water, and residential pathways, the combined or aggregate exposures are estimated and 

expressed in terms of an aggregate MOE. The aggregate MOE is compared with the target MOE 

to determine whether there is an aggregate exposure of concern. All routes of diquat dibromide 

exposure were considered in the aggregate assessment for this TRED. Aggregate exposure 

pathways for adults include dietary, drinking water, and dermal exposures from application and 

post-application activities. Aggregate exposure pathways for children include dietary, drinking 

water, oral and dermal exposures from post-application exposure. A target MOE of 100 is 

considered adequate for aggregate exposure/risk. Acute and chronic aggregate MOEs were not a 

risk concern, nor was the short term aggregate MOE for adults. The short-term screening level 

aggregate MOE for the toddler (child 1-6) exposure scenario was 55. The short-term aggregate 

risk combines screening level risk estimates from individual exposure pathways and should be 

viewed as a highly conservative estimate which is certain to over-estimate risk. A refined analysis 

would result in lower exposure estimates and higher MOEs. 

Data Gaps

All product chemistry data are required for the Syngenta 41.1% and 37.3% Formulation 

Intermediates (EPA Reg. Nos. 10-1062 and 100-1063). Magnitude of the residue in plants studies 

are required for sorghum aspirated grain fractions and soybean aspirated grain fractions. 

2.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

Common Name: Diquat Dibromide 

Chemical Name: 6,7-dihydrodipyrido(1,2-a;2',1'-c)pyrazinediium dibromide

Trade Names: Reglone, Weedkiller D, Aquacide, Dextrone, FB 2, Reglox, Reward 

Empirical Formula: C12H12Br2N2

CAS No.: 85-00-7

PC Code: 032201

Structure: 
 9  44

Molecular Weight: 344 [Cation - 184]

Physical State: Crystals

Color: Colorless to Yellow

Odor: Odorless

Solubility in Water: 700 g/L at 20C

Vapor Pressure: < 0.03 mPa

Melting Point: 300C

Density: 1.22-1.27 at 20C

Pure diquat dibromide is an odorless, colorless to yellow crystal. It is very soluble in 

water, slightly soluble in alcohol and hydroxylic solvents, and insoluble in non-polar organic 

solvents. It is susceptible to ultraviolet decomposition. Ethylene dibromide (EDB) may be present 

as a process impurity in final formulations of diquat dibromide. However, the registrant has 

certified an upper limit of 10 ppm EDB in diquat dibromide and has demonstrated that EDB does 

not persist as an impurity in diquat dibromide and will slowly dissipate over time. 

3.0 HAZARD CHARACTERIZATION

3.1 Hazard Profile

The toxicity data base for diquat dibromide is adequate for the selection of doses and 

endpoints for use in risk assessment. HED’s Hazard Identification Assessment Review Committee 

(HIARC) evaluated the acceptable studies available in the database and established acute and 

chronic reference doses (RfD), as well as doses and endpoints for short and intermediate-term 

incidental oral exposure, and short-term, intermediate-term, and long-term dermal and inhalation 

exposure scenarios. The Acute Reference Dose (Acute RfD) is an estimate (with uncertainty

spanning an order of magnitude or greater) of a single day oral exposure level for the human 

population, including the sensitive subpopulations, that is likely to be without an appreciable risk 

of deleterious effects. The Chronic Reference Dose (Chronic RfD) is an estimate (with 

uncertainty spanning an order of magnitude or greater) of a daily oral exposure level for the human 

population, including sensitive subpopulations, that is likely to be without an appreciable risk of 

deleterious effects during a lifetime. The acute RfDs are calculated by dividing the NOAEL by

the Uncertainty Factors (UF). Uncertainty Factors are used to account for differences between 

humans (intraspecies variability) and for differences between the test animals and humans 

(interspecies extrapolation). For residential exposures, uncertainty factors are used to determine 

adequate margins of exposure (MOEs). The MOE is the ratio of the route appropriate NOAEL to 

estimated exposure. The HIARC also evaluated available studies to determine if there is a special 

sensitivity for infants and children. The toxicological data are summarized below. 
 10  44

3.1.1 Acute Toxicity

Diquat dibromide 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-to-severely toxic via the dermal route of exposure (Toxicity Categories I for technical 

and II for formulation). Diquat dibromide is not an acute skin irritant (Toxicity Category IV) nor a 

dermal sensitizer, but it is considered a moderate-to-severe eye irritant (Toxicity Category II). 

Acute toxicity categories for diquat are shown in Table 1.

Table 1. Acute Toxicity Data on DIQUAT DIBROMIDE

Guideline No. Study Type MRID #(S) Results Toxicity Category

870.1100 acute oral - rat 

Diquat Water Weed Killer

00081506 rat LD50 = 810 mg/kg 

rat LD50 = 600 mg/kg 

III

870.1200 acute dermal - rat

Diquat Water Weed Killer

00100614 rabbits LD50 = 262 mg/kg 

rabbits LD50 = 315 mg/kg 

rabbits LD50 = 288.5 mg/kg +

II

870.1300 acute inhalation - rat

Diquat Water Weed Killer

26385 rat LC50 = 0.80 mg/L 

rat LC50 = 1.09 mg/L 

rat LC50 = 0.97 mg/L +

III

870.2400 primary eye irritation -

Diquat Water Weed Killer

00081507 rabbit slight to severe eye irritant II

870.2500 primary skin irritation -

Diquat Water Weed Killer

00107903 slight irritation IV

870.2600 Dermal Sensitization 00107903 not a dermal sensitizer N/A

  Accession No.; 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 end-use products is 2.15% of 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 not, as is commonly done with diquat, in terms of the diquat cation.

3.1.2 Toxicity Profile

Table 2 identifies and summarizes guideline studies conducted for diquat dibromide.

.

Table 2. Toxicity Profile of DIQUAT DIBROMIDE

GUIDELINE STUDY MRID RESULTS

OPPTS 870.3100 90-day oral toxicity - rat no study available

OPPTS 870.3150 subchronic nonrodent oral toxicity - 90-day no study available

OPPTS 870.3200 repeated dose dermal toxicity -21/28 days - rat

20.64% diquat cation

[doses: 0, 5, 20, 40, and 80 mg/kg/day]

40308101 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 doserelated mortality and clinical signs [hypothermia, 

hypoactivity, dyspnea, cyanosis, pale extremities, general 

poor condition, and emaciated appearance]. Based on the 
 11  44

Table 2. Toxicity Profile of DIQUAT DIBROMIDE

GUIDELINE STUDY MRID RESULTS

Classification: Acceptable/Guideline

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

OPPTS 870.3200 repeated dose dermal toxicity -20 days - rabbit

[doses: 20, 40, 80, 160 mg diquat cation/kg/day]

Classification: Acceptable/Non-Guideline

00140576 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].

OPPTS 870.3250 subchronic dermal toxicity - 90 days no study available

OPPTS 870.3465 subchronic inhalation toxicity [21-day]

21.6% and 23.5% diquat cation

[doses: 0, 0.49, 1.1, 3.8 μg/L; 0, 0.1 μg/L]

Classification: Acceptable/Guideline, when both studies 

are considered together. NOTE: Duration of study is 21 

days, not 90 days.

40301701 

40640801

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].

OPPTS 870.3500 preliminary developmental toxicity screen no study 

OPPTS 870.3600 inhalation developmental toxicity study no study

OPPTS 870.3700 prenatal developmental toxicity study - rat

26.2% diquat cation

[doses: 0, 4, 12, 40 mg/kg/day]

Classification: Acceptable/Guideline

41198902 Maternal NOAEL: 4 mg/kg/day

Maternal LOAEL: 12 mg/kg/day, based on decreased bodyweight gains and food consumption during dosing. At HDT, 

there was one death [GD 15], and clinical signs [piloerection 

and subdued activity] were observed [GD 13-22].

Developmental NOAEL: 12 mg/kg/day 

Developmental LOAEL: 40 mg/kg/day, based on decreased 

fetal, litter, and gravid uterine weights, an increased incidence 

of fetuses with hemorrhagic kidney, and delayed skeletal 

ossification [increased incidence of minor skeletal variations, 

including unossified ventral tubercle, unossified cervical 

vertebral centra, and delayed ossification of the 2nd and 5th 

sternebrae].

OPPTS 870.3700 prenatal developmental toxicity study - rabbit

26.2% diquat cation

[doses: 0, 1, 3, 10 mg/kg/day]

41198901 Maternal NOAEL: 1 mg/kg/day

Maternal LOAEL: 3 mg/kg/day, based on body-weight loss 

[GD 7-10] and decreased food consumption [GD 7-10]. At 

HDT, there were deaths and clinical signs [diarrhea, subdued 

activity, thin appearance, mucus, blood, little or no feces in 

tray]

Developmental NOAEL: 3 mg/kg/day 

Developmental LOAEL: 10 mg/kg/day, based on decreased 

fetal body weight, an increased incidence of friable/mottled 

livers, and an increased incidence of minor skeletal alterations 

[partially ossified ventral tubercle of cervical vertebrae, 

partially ossified 6th sternebrae, and unossified 6th sternebrae 
 12  44

Table 2. Toxicity Profile of DIQUAT DIBROMIDE

GUIDELINE STUDY MRID RESULTS

Classification: Acceptable/Guideline and presacral vertebrae].

OPPTS 870.3700 prenatal developmental toxicity study - mouse

analytical standard

[doses: 0, 1, 2, 4 mg/kg/day]

Classification: Acceptable/Non-Guideline

00061637 Maternal NOAEL: 1 mg/kg/day [as diquat cation]

Maternal LOAEL: 2 mg/kg/day, based on mortality, clinical 

signs [piloerection, respiratory sounds], and decreased bodyweight gain [during dosing period]. At HDT, additional 

clinical signs [abnormal posture (hunched or tail raised), 

lethargy, tremors, unsteadiness on feet, emaciation, ptosis] 

and a slight decrease in body weight [91% of control] at 

termination were observed also. NOTE: Poor dosing 

technique; incidental exposure into lungs.

Developmental NOAEL: 2 mg/kg/day 

Developmental LOAEL: 4 mg/kg/day, based on decreased 

fetal body weight and an increased incidence of overall 

skeletal alterations.

OPPTS 870.3800 reproduction and fertility effects

20.09% diquat cation

[doses: 0, 16, 80, 400/240 ppm (0, 0.8, 4, 20/12 

mg/kg/day)]

Classification: Acceptable/Guideline

41531301

Parental NOAEL: 16 ppm [0.8 mg/kg/day]

Parental LOAEL: 80 ppm [4 mg/kg/day], based on clinical 

signs, ulceration of the tongue, and partial/total cataract. At 

HDT, increased incidence of clinical signs including 

ophthalmoscopic signs and lack of grooming, and gross and 

microscopic findings [ulceration of the tongue and 

partial/total cataract].

Reproductive/Developmental NOAEL: 80 ppm [4 mg/kg/day]

Reproductive/Developmental LOAEL: 400/240 ppm [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.

OPPTS 870.4100 chronic toxicity [feeding] study - beagle dog

26.7% diquat cation

[doses: 0, 0.5, 2.5, 12.5 mg/kg/day for 52 weeks]

Classification: Acceptable/Guideline

41730301 NOAEL: 0.5 mg/kg/day 

LOAEL: 2.5 mg/kg/day, based on unilateral cataracts in 

females, and decreased weights of epididymides and adrenals 

in males. At the HDT, bilateral lenticular opacity [cataracts], 

macroscopically and microscopically [in all dogs, both sexes]; 

inflammatory lesions in the large intestine [in all dogs, both 

sexes]; increased kidney weight [both sexes].

OPPTS 870.4200 carcinogenicity -CD-1 mouse

21.09% diquat cation

[doses: 0, 30, 100, 300 ppm (males 0, 3.56, 11.96, 

37.83 mg/kg/day; females 0, 4.78, 16.03, 48.27 

mg/kg/day)] for 104 weeks

Classification: Acceptable/Guideline

42219801 

42880701 

42905901 

42919501

NOAEL = 30 ppm [356/4.78 mg/kg/day]

LOAEL: 100 [11.96/16.03 mg/kg/day], based on clinical 

signs [eye discharge (males), subdued behavior (females)], 

and decreased body weight/body-weight gain [males]. Diquat 

dibromide was not carcinogenic in male or female CD-1 mice.

OPPTS 870.4300 combined chronic toxicity/carcinogenicity - rat

26.5% diquat cation

[doses: 0, 5, 15, 75, and 375 ppm (0, 0.19, 0.58, 2.91, 

and 14.88 mg/kg/day for males and 0, 0.24, 0.72, 3.64, 

and 19.44 mg/kg/day for females)] for 104 weeks. 

Classification: Acceptable/Guideline

00145855 

00155474 

41085601

NOAEL: 15 ppm [0.58/0.72 mg/kg/day]

LOAEL: 75 ppm [2.91/3.64 mg/kg/day], 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. 

OPPTS 870.5100-

5915

genetic toxicity tests 

Classification: Acceptable/Guideline

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. Also, 

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.
 13  44

Table 2. Toxicity Profile of DIQUAT DIBROMIDE

GUIDELINE STUDY MRID RESULTS

OPPTS 870.6100 delayed neurotoxicity of OPs following acute/28-day 

exposures

- no study

OPPTS 870.6200 neurotoxicity screening battery - acute [rat]

20.1% diquat cation

[doses: 0, 25, 75, and 150 mg/kg]

Classification: Acceptable/Guideline

42666801 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 sides] and 

decreased body-weight gains.

NOTE: Agency concluded that signs may not be due to direct 

neurotoxicity.

OPPTS 870.6200 subchronic neurotoxicity - Alpk:APfSD rats

20.8% diquat cation

doses: 0, 20, 100, and 400 ppm [males 0, 1.6, 8.0, 32.4 

mg/kg/day/females 0, 1.9, 9.5, and 38.5 mg/kg/day]

Classification: Acceptable/Guideline

42616101 Systemic Toxicity NOAEL = 100 ppm [8.0/9.5 mg/kg/day

Systemic Toxicity LOAEL = 400 ppm [32.4/38.5 mg/kg/day, 

based on evidence of cataracts and decreased body-weight 

gain and food utilization in both sexes. There was no 

evidence of neurotoxicity at any dose level.

OPPTS 870.6300 developmental neurotoxicity study - no study

OPPTS 870.7485 metabolism and pharmacokinetics [disposition and 

metabolism]

Classification: Acceptable/Guideline when considered 

with other two studies

00065592 Diquat dibromide 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. 

Metabolism - excretion

Classification: Acceptable/Guideline when considered 

with other two studies

00065593 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 [5.3%] 

of the [

14C] was unchanged Diquat, 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 acidextractable 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%]. 

Metabolism

Classification: Acceptable/Guideline when considered 

with other two studies

00055107 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.

OPPTS 870.7600 dermal penetration

Classification: Acceptable/Guideline 41238701

dermal absorption of Diquat dibromide through intact rat skin 

is considered very low.

OPPTS 870.7800 immunotoxicity - no study

3.1.3 Hazard Characterization
 14  44

The toxicity data base for diquat is complete and clearly defines the toxicity of the 

compound. Subchonic and chronic studies in several species indicate multiple target sites for 

diquat dibromide toxicity. In subchronic dermal exposure studies in rats, diquat dibromide showed 

evidence of severe systemic toxicity, i.e. high mortality and clinical signs. While a dermal study

was available, the dermal endpoint is based on a rabbit developmental gavage study because the 

dermal study was determined to be inappropriate for endpoint selection. Route specific endpoints 

are available for all other exposure pathways. In a subchronic inhalation study in rats, the lung was 

determined to be the primary target site for inhalation toxicity. Chronic feeding studies in dogs, 

rats, and mice indicate that target sites include the eyes and kidneys in both males and females and 

the adrenals and epididymides in males. Developmental toxicity was observed in rat, rabbit, and 

mouse studies, and reproductive toxicity was observed in the rat in both generations. Rat and 

rabbit studies provided evidence of maternal toxicity. The acute and subchonic neurotoxicity

studies in rats provided no evidence of neurotoxicity. Available data provide no evidence of 

endocrine disruption following exposure to diquat dibromide. Carcinogenicity studies in rats and 

mice provided no evidence of increase tumor incidence and diquat dibromide was classified as a 

Category E (evidence of non-carcinogenicity to humans) by the HED Reference Dose (RfD)/Peer 

Review Committee based on the 1999 EPA Draft Proposed Guidelines for Carcinogen Risk 

Assessment. The weight of the evidence was predominantly negative for mutagenicity. The data 

provided no indication of increased sensitivity of rats, mice, or rabbits to in utero and/or early

postnatal exposure to diquat dibromide. The terminal residue of concern is the parent compound, 

diquat cation. There is no indication that metabolites are present in significant quantities. 

3.2 FQPA Considerations

HED’s FQPA committee determined that the FQPA safety factor could be removed (1x) in 

assessing the risk posed by this chemical because the toxicological database is complete for FQPA 

assessment, there is no indication of quantitative or qualitative increased susceptibility of rats or 

rabbits to in utero and/or postnatal exposure, a developmental neurotoxicity study is not required, 

and the dietary (food and drinking water) and residential exposure assessments will not 

underestimate the potential exposures for infants and children. The HIARC and FQPA Committee 

determined that a developmental neurotoxicity study was not required for diquat dibromide based 

on the fact that (1) there is no indication of abnormalities in the development of the fetal nervous

system in prenatal developmental toxicity studies in rats, mice, and rabbits at oral dose levels that 

were maternally toxic, (2) there was no evidence of neuropathology in either the acute or 

subchronic neurotoxicity studies, (3) the clinical and functional observational battery observations 

in the acute neurotoxicity study, which could not be unequivocally correlated to an effect on the 

nervous system, were not observed in the subchronic neurotoxicity study, and (4) no neurotoxic 

effects were observed in the brain weights or histopathology of the nervous system in the chronic 

toxicity studies with diquat in several species.

3.3 Dose Response Assessment

Doses and toxicological endpoints selected for various exposure scenarios are summarized 

in Table 3. 

Table 3. Summary of Toxicological Dose and Endpoints for Diquat for Use in Human Risk Assessment
 15  44

Exposure Scenario Dose Endpoint Study

Acute Dietary

general population

incl infants and 

children

NOAEL= 75 mg/kg 

UF = 100

LOAEL of 150 mg/kg based on clinical signs and 

decreased body-weight gain. 

Acute 

neurotoxicity

rat

FQPA = 1x Acute RfD = 0.75 mg/kg Acute PAD = 0.75 mg/kg

Chronic Dietary

NOAEL = 0.5 

mg/kg/day

UF = 100

LOAEL of 2.5 mg/kg/day based on cataracts in 

females and decreased adrenal and epididymides 

weights in males. 

chronic toxicity 

dog

FQPA = 1x Chronic RfD = 0.005 mg/kg/day Chronic PAD = 0.005 mg/kg/day

Short-Term Oral

(1day - 1 month)

NOAEL = 1 mg/kg/day 

MOE = 100

LOAEL of 3 mg/kg/day based on body-weight loss 

and decreased food consumption. 

Developmental 

toxicity -

rabbit

Short-Term

Dermal a 

(1 day - 1 month)

NOAEL = 1 mg/kg/day 

MOE = 100

LOAEL of 3 mg/kg/ day based on body-weight loss 

and decreased food consumption.

Developmental 

toxicity -

rabbit

Short-Term

Inhalation

(1 day - 1 month)

NOAEL = 0.1 ug/l 

(0.024 mg/kd/d male, 

0.026 mg/kd/d female)

MOE = 100

LOAEL of 0.49 ug/L (0.117 mg/kg/day male, 

0.128female) due to increased mean lung weight in 

males, mottling and reddening of lungs in females, 

and lung lesions. 

21-day 

inhalation 

toxicity

rat

a

Since an oral value was selected, route-to-route extrapolation should be followed. A dermal absorption factor is required for this risk assessments.

3.3.1 Dietary Exposure Endpoints

3.3.1.1 Acute Reference Dose

The HIARC selected an acute RfD of 0.75 mg/kg based on an acute neurotoxicity gavage 

study in the rat which showed clinical signs of systemic toxicity (e.g., piloerection, diarrhea, 

urinary incontinence, upward curvature of the spine, subdued behavior) and decreased body-weight 

gains at the systemic Lowest Observed Adverse Effect Level (LOAEL). The study is considered 

appropriate for selection of an acute endpoint because effects were seen after a single dose. The 

HIARC recommended a (UF) of 100x (10x for interspecies and 10x for intraspecies is 

extrapolation) for calculation of the RfD. 

The acute endpoint selected by the HIARC for the current risk assessment differs from that 

used in assessments conducted for the 1995 RED and 1998 assessment of risk based new and 

revised uses. The acute dietary endpoint used in previous assessments was based on a rat 

developmental study, which showed transitory decrease in mean body-weight gain of the maternal 

rat following four days of exposure to diquat dibromide. The HIARC concluded that this endpoint 

was not a single dose effect and so was not appropriate for use in an acute risk assessment. The 

rabbit and mouse developmental toxicity studies were also re-evaluated by the HIARC for the 

current analysis. The rabbit study was deemed inappropriate because the maternal body-weight 

loss observed during gestation was not a single dose effect. The mouse study was rejected for 
 16  44

endpoint selection because of poor dosing technique which caused inappropriate introduction of 

test material into the lungs. 

3.3.1.2 Chronic Reference Dose

The HIARC selected a chronic RfD of 0.005 mg/kg/day from a chronic oral dog toxicity 

study. The endpoint is based on unilateral cataracts in males and females and decreased adrenal 

and epididymides weights in males at the LOAEL of 2.5 mg/kg/day. The study is considered 

appropriate for selection of an endpoint for a chronic exposure scenario because cataracts and 

decreased adrenal and epididymides weights are found consistently in repeat exposure studies in 

both the dog and the rat. The rat chronic toxicity/carcinogenicity study which also showed 

evidence of cataracts, was considered co-critical for this endpoint. The HIARC recommended a 

UF of 100 (10 interspecies; 10 intraspecies). The chronic endpoint selected for the current analysis 

was used in both of the previous diquat risk assessments. 

3.3.2 Residential Exposure Endpoints

3.3.2.1 Short-Term Oral Exposure (1 day - 1 month)

A short-term oral NOAEL of 1 mg/kg/day was selected from a rabbit developmental gavage

study which showed maternal body-weight loss during gestation days (GD) 7-10 and decreased 

food consumption during dosing (GD 7-10) at the LOAEL of 3 mg/kg/day. The study is 

considered appropriate as a basis for endpoint selection for infants and children, the population of 

concern for incidental oral exposure. A target MOE of 100 was determined to be adequate for this 

exposure pathway by the HIARC. A short-term oral endpoint was not included in previous HIARC

or risk assessment documents for this chemical. 

3.3.2.2 Short-Term Dermal Exposure (1 day - 1 month)

The HIARC selected a short-term dermal NOAEL of 1 mg/kg/day. The endpoint is based 

on a rabbit developmental gavage study which resulted in maternal body-weight loss during 

Acute RfD = 75mg/kg (NOAEL 100 (UF) = 0.75 mg/kg

Chronic RfD = 0.5mg/kg/day 100 (UF) (NOAEL) = 0.005 mg/kg/day
 17  44

gestation days (GD) 7-10 and decreased food consumption during dosing (GD 7-10) at the LOAEL 

of 3 mg/kg/day. The rat chronic toxicity/carcinogenicity study was considered co-critical for this 

endpoint. The recommended target MOE was 100. For the diquat risk assessment conducted for 

the 1995 RED, and endpoint from a 20 day dermal toxicity study in rabbits was selected for use in 

assessing risk from dermal exposure. For the 1998 revised assessment, the HIARC determined that

the 21-day rat dermal toxicity study was more appropriate for use in selecting a dermal endpoint 

because the rabbit study is a non-guideline study. Only 3 rabbits/group were used and hematology, 

clinical chemistry, and urinalysis parameters were not monitored. The guideline states that ten 

animals/sex/dose are needed for a NOAEL for risk assessment. The HIARC then re-evaluated the 

rat dermal toxicity study for this TRED. Based on the most recent review, the HIARC concluded 

that the rat study was inappropriate for use in endpoint selection because the animal’s skin was 

compromised resulting in increased severity of effects and an artificially low NOAEL. 

3.3.2.3 Dermal Absorption

Since the dermal exposure endpoints were selected from oral toxicity studies, a dermal 

absorption factor is required to convert the oral dose to an equivalent dermal dose for the risk 

assessment. In an acceptable/guideline in vivo per cutaneous absorption study, three aqueous doses 

of [14C] diquat dibromide were applied dermally to 12 Sprague-Dawley rats (four rats per dose). 

The rats were dermally dosed at levels of 0.05, 0.5, and 5 mg diquat cation/rat for exposure periods 

of 2, 10 and 24 hours. The respective 2, 10, and 24 hour absorption rates were 4.1, 5.5, and 7.4% 

at the low dose (0.05 mg/rat), absorption was 2.8, 5.3, and 4.7% at the middle dose (0.5 mg/rat), 

and 2.6, 2.5, and 3.3% at the high dose (5 mg/rat). (Total percent absorbed = percent absorbed + 

percent remaining in/on the skin.) 

The 4.1% (dermal absorption factor corresponding to the 2 hour, low dose (0.05 mg/rat) 

exposure was used for the non-occupational handler and postapplication exposure scenarios where 

children and adults are assumed to have a 2 hour exposure duration. This is a conservative 

assumption in which total percent absorbed = percent absorbed (1.2%) + percent remaining in/on 

the skin (3.9%). 
 18  44

3.3.2.4 Short Term Inhalation Exposure (1 day - 1 month)

The selected NOAEL for inhalation exposure is 0.1 μg/L (0.023 mg/kd/day male, 0.027 

mg/kg/day female) based on a repeated dose 21-day inhalation toxicity study in rats which resulted 

in on increased lung weights and microscopic lesions in the lungs at the LOAEL of 0.49 μg/L 

(0.113 mg/kg/day male, 0.134 female). The route and duration of exposure are appropriate for 

selecting a short term inhalation endpoint. 

3.3.2.5 Intermediate and Long-Term Endpoints - The HIARC also selected endpoints for 

intermediate-term oral, and intermediate, and long-term dermal and inhalation exposure scenarios. 

However, since only short-term exposures are anticipated for residential uses, endpoints for longer 

term exposures were not used in the exposure and risk assessments for this TRED.

3.3.2.6 Common Toxicological Endpoints for Exposure Routes

A common toxicological endpoint (decrease in maternal body weight and food 

consumption) was selected for assessment of short-term incidental oral and dermal (oral 

equivalent) exposures. Therefore, these exposure routes can be aggregated. The toxicological 

endpoint (increased lung weight and microscopic lung lesions) observed via the inhalation route is 

unique. Therefore, this exposure route cannot be aggregated with the oral and dermal exposures.

3.4 Endocrine Disruptor Effects

Available toxicity data suggest that there is no evidence of endocrine disruption following 

exposure to diquat dibromide. EPA is required under the FFDCA, as amended by FQPA, to 

develop a screening program to determine whether certain substances (including all pesticide 

active and other ingredients) "may have an effect in humans that is similar to an effect produced by

a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." 

Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory

Committee (EDSTAC), EPA determined that there was scientific bases for including, as part of the 

program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. 

EPA also adopted EDSTAC’s recommendation that the Program include evaluations of potential 

effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in 

wildlife may help determine whether a substance may have an effect in humans, FFDCA authority

to require the wildlife evaluations. As the science develops and resources allow, screening of 

additional hormone systems may be added to the Endocrine Disruptor Screening Program (EDSP).

When the appropriate screening and/or testing protocols being considered under the 

Agency’s EDSP have been developed, diquat dibromide may be subjected to additional screening 

and/or testing to better characterize effects related to endocrine disruption.
 19  44

4.0 EXPOSURE ASSESSMENT

4.1 Summary of Registered Uses

Currently registered uses are summarized in Table 4. Table 5 summarizes the volume of 

diquat dibromide usage by crop.

Table 4. Diquat Dibromide Use Groups and Sites

Use Group Use Sites

Aquatic Food Crop agricultural drainage & irrigation systems; lakes/ponds/reservoirs with human or 

wildlife use 

Aquatic Non-food 

Industrial

drainage systems, lakes/ponds/reservoirs without human or wildlife use

Aquatic Non-food 

Outdoor

aquatic and intermittently flooded areas, streams/rivers/channeled water 

Aquatic Non-food 

Residential

ornamental ponds/aquaria

Greenhouse Food Crop in-use greenhouse

Indoor Food storage areas - empty and full

Indoor Non-food empty greenhouse

Outdoor Residential residential lawns, household/domestic dwellings outdoor premises

Terrestrial Feed Crop alfalfa, Bermuda grass, clover

Terrestrial Non-Food 

Crop

carrot, cucumber, melons, pepper, radish, squash, turnip, tomato

Terrestrial Food & Feed 

Crop

potato, sorghum, soybeans

Terrestrial Non-food 

Crop

agricultural fallow/idleland, structures/equipment, rights-of way/fence rows/hedge rows, 

and uncultivated areas; airports/landing fields; commercial/industrial lawns, premises 

and equipment (outdoor); golf course turf; nonagricultural outdoor structures/rights-ofway/fence rows/hedge rows

Table 5. Volume of Diquat Dibromide Usage by Crop

Crop % Treated

Pounds A.I. 

(1000)

Application Rate (lbs 

A.I) Major States

Alfalfa/Seed 50 25 0.4 CA, OR, WA

Potatoes 30 170 0.3 ME, ND, NY

Soybeans <1 1 0.4 -

Sorghum <1 2 0.4 -

Dry Beans <1 1 0.3 -
 20  44

Table 5. Volume of Diquat Dibromide Usage by Crop

Crop % Treated

Pounds A.I. 

(1000)

Application Rate (lbs 

A.I) Major States

Grapes <1 1 0.4 -

Home & Garden <1 100 0.3 -

Aquatic Uses <1 200 1.5 CA, FL

Total 500 

4.2 Dietary Exposure/Risk Pathway

4.2.1 Residue Profile

4.2.1.1 Nature of the Residue - Plants and Livestock

Plants

The reregistration requirements for plant metabolism are fulfilled (T. Morton, 11/20/01, 

D277710). The qualitative nature of the residue in plants 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, 11/8/01, D277765). The established tolerance expression 

for residues of diquat dibromide in/on plant 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, the Agency 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. The retention of 

diquat residues in tissues was negligible (0.004 ppm diquat equivalents) following dosing at 

25x the maximum human dietary intake.

Livestock

The reregistration requirements for animal metabolism are fulfilled. The qualitative nature 

of the residue in livestock is adequately understood based on acceptable poultry, ruminant, and fish 

metabolism studies. The HED Metabolism Assessment Review Committee (MARC) has 

concluded the residue of concern for livestock is the diquat cation (T. Morton, 11/8/01, D277765). 
 21  44

The established tolerance expression for residues of diquat dibromide in animal commodities is 

appropriate and no changes are required.

In the poultry metabolism study, laying hens were dosed with ring-labeled [14C]diquat at 32 

ppm in the diet for 4 days. The total radioactive residues (TRR; expressed as diquat equivalents) 

ranged from <0.001-0.004 ppm in egg yolks, egg whites, fat, and muscle, 0.042-0.058 ppm in 

kidney, and 0.030-0.045 ppm in liver. The predominant metabolites identified were diquat cation 

(48% of TRR in liver), and diquat monopyridone (15.1% of TRR in kidney) 

The metabolism of diquat dibromide in ruminants has been extensively investigated. 

Ruminant data confirm that the residue of concern in ruminant milk and tissues is diquat cation. 

Ethylene bridge-labeled [14C]diquat dibromide was administered at 5 ppm to three cows. In 

addition, one cow was dosed with ethylene bridge-labeled [14C]diquat at 20 ppm and with 

bypyridyl-labeled [14C]diquat at 5 ppm. The highest TRR value in milk was 0.077 ppm in the 72-

hour milk sample from the cow dosed at 20 ppm. In milk samples from the high-dose cow, 

residues of diquat per se were quantitated at <0.002 ppm and did not concentrate in the fat, casein 

or whey. No residues (<0.01 ppm) were found in the leg muscle samples from one of the cows 

dosed at 5 ppm. A bull calf was administered ethylene bridge-labeled [14C]diquat dibromide at 8 

ppm and sacrificed 24 hours after dosing. The TRR were 1.071 ppm in kidney, 0.033 ppm in liver 

and <0.04 ppm in other tissues. Residues of diquat cation were 0.03 ppm and <0.01 ppm in the 

kidney and liver samples, respectively.

In the fish metabolism study, trout and carp were exposed to an initial concentration of 1 

ppm of bridge-labeled [14C]diquat in the water for 7 days. The TRR (expressed as diquat 

equivalents) in carp head and tail, viscera, and body with skin were 0.025-0.077 ppm, 0.135-0.946 

ppm, and 0.013-0.024 ppm, respectively. The TRR in skin and flesh without skin were 0.015-

0.023 ppm and 0.006-0.016 ppm, respectively. The TRR in trout head, tail, and flesh were 

0.025-0.051 ppm, 0.059-0.239 ppm, and 0.008-0.01 ppm, respectively. Approximately 65% of the 

radioactivity in carp flesh and trout viscera was identified as diquat. 

4.2.1.2 Residue Analytical Method - Plants and Livestock

Enforcement methods

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

designated as Method A as available for the enforcement of tolerances for residues of diquat in/on 

plant and in livestock commodities. The limit of detection is 0.01 ppm. The registrant has 

proposed new enforcement methods, RM-5B-1 and RM-5C, for plant and livestock commodities, 

respectively. The stated limit of detection is 0.005 ppm for RM-5B-1; the limit of detection for 

RM-5C is not clearly specified. Both methods have been adequately validated by the registrant; 

however, an independent laboratory validation must be conducted followed by validation by the 

Agency's Analytical Chemistry Branch before they can be considered fully adequate for 
 22  44

enforcement purposes. Once a successful EPA method validation has been performed, these 

methods will be sent to FDA for inclusion in PAM Vol. II.

Data collection

Residue data submitted for tolerance reassessment were collected using the current (PAM 

Vol. 2 Method A) or proposed (RM-5B and RM-5C) enforcement methods. The registrant 

provided adequate method validation data to verify the suitability of these methods for data 

collection.

4.2.1.3 Multiresidue Methods

The FDA's PESTDATA dated 11/6/90 (PAM Vol. I, Appendix) indicates that recovery of 

diquat dibromide using Multiresidue Protocols is unlikely. The updated PESTDATA dated 08/93 

does not have an entry for diquat dibromide.

4.2.1.4 Storage Stability Data

The requirements for storage stability data are fulfilled for purposes of tolerance 

reassessment. Adequate storage stability data on diquat dibromide are available to support the 

storage conditions and intervals of samples from magnitude of the residue studies in plants and 

livestock. Residues of diquat are stable under frozen (-20C) storage conditions for: up to six 

months in/on bell pepper, carrot roots, clover (hay and seed), lettuce, potato, rice (grain and straw), 

sorghum grain, soybean, tomato and tomato processed fractions, and wheat (grain and straw); up to 

8 months in processed fractions of sorghum grain and soybean; and up to 2 months in water and 

seafood samples.

4.2.1.5 Magnitude of the Residue in Crop Plants

All data for magnitude of the residue in plants have been evaluated and deemed adequate 

except for the following deficiencies: residue data required for sorghum aspirated grain fractions, 

soybean aspirated grain fractions. All field residue data have been re-evaluated and plant 

commodity tolerances reassessed (where residue data are available) for TRED purposes. There are 

no registered uses of diquat dibromide on sugarcane and vetch. Therefore, field residue data for 

these crops are no longer required and the established tolerance for residues in/on sugarcane should 

be revoked.

4.2.1.6 Magnitude of the Residue in Processed Food/Feed

The data for magnitude of the residue in processed food/feed have been evaluated and 

deemed adequate to determine the extent to which residues of diquat concentrate in food/feed 

items upon processing of raw agricultural commodities. Acceptable potato, soybean, and sorghum 

processing studies have been submitted and evaluated. Acceptable processing data are also 
 23  44

available for tomato wet pomace, tomato juice, and tomato paste. However, additional residue 

data are required for sorghum and soybean aspirated grain fractions and tomato puree.

4.2.1.7 Magnitude of the Residue in Meat, Milk, Poultry, and Eggs

The reregistration data requirements for magnitude of the residue in livestock are fulfilled. 

The HED MARC has concluded that the residue of concern for livestock is the diquat cation (T. 

Morton 11/08/01) and acceptable animal feeding studies have been submitted and evaluated. 

A new maximum dietary burden (MDB) estimate has been calculated based on reassessed 

established/proposed tolerances of feed commodities and revised Table II of OPPTS 860 

Guidelines. (T. Morton, 11/20/01, D277710). The established tolerances of 0.02 ppm for diquat 

residues in the fat, meat, and meat byproducts of cattle, goats, hogs, horses, and sheep may be 

raised to 0.05 ppm to achieve compatibility with the Codex maximum residue limit (MRL). The 

established 0.02-ppm tolerance level for diquat residues in poultry fat, meat, meat byproducts and 

eggs may be raised to 0.05 ppm to achieve compatibility with the Codex MRL. 

4.2.1.8 Magnitude of the Residue in Fish and Shellfish

All data requirements for magnitude of the residue in fish and shellfish have been evaluated 

and deemed adequate to reassess the tolerances for diquat; no additional data are required 

regarding this topic. The available data indicate that residues of diquat in fish and shellfish will 

exceed the established tolerances following tests reflecting the current maximum registered use 

patterns. The registrant must submit a petition requesting tolerance increases from 0.1 ppm to 2.0 

ppm for fish and 20 ppm for shellfish to cover all residues of diquat which may occur as a result of 

the currently registered uses.

4.2.1.9 Magnitude of the Residue in Irrigated Crops

The available data concerning diquat residues following irrigation of carrot, corn (sweet), 

cowpea, peach, and rice are adequate to support the established 0.02 ppm tolerances for diquat 

residues in/on all members of the crop groups containing these commodities. However, the data 

also indicate that residues in/on cowpea, blackberry, strawberry, orange, mustard greens, pasture 

grass, and tomato may exceed the tolerances for the respective crop groups. The registrant must 

propose a higher tolerance level of 0.05 ppm for citrus fruit, small fruits, fruiting vegetables, 

legume vegetables, and Brassica leafy vegetables. The registrant is required to propose a higher 

tolerance level of 0.20 ppm for forage grasses.

No data are available for the commodities avocado, cottonseed, hops, and sugarcane for 

which tolerances currently exist. However, data for other crops can be translated to these 

commodities. Based on the highest residues found in other crops irrigated with water containing 

diquat residues, HED recommends that the registrant propose tolerances of 0.20 ppm for these 

crops. If lower tolerances are desired, additional data will be required. 
 24  44

4.2.1.10 Confined and Field Accumulation in Rotational Crops

The data requirements for confined rotational crops have been reviewed and deemed 

adequate by the Environmental Fate and Effects Division (EFED). The requirements for field 

rotational crop studies have been waived at this time.

4.2.1.11 Codex/International Harmonization

Several maximum residue limits (MRLs) for diquat have been established by Codex in 

various commodities. Tolerance levels for some commodities with an MRL have been revised in 

the TRED to achieve compatibility with Codex. The U.S. tolerance for eggs, poultry, meat, and 

offal (mammalian) may be raised to 0.05 ppm to achieve harmonization. Further harmonization of 

U.S. tolerances and Codex MRLs on other commodities are not feasible at this time because of 

differences in agricultural practices. 

4.2.2 Dietary Exposure/Risk Assessment

4.2.2.1 Consumption Data and Dietary Risk Analysis

Diquat acute and chronic dietary exposure assessments were conducted using the Dietary

Exposure Evaluation Model (DEEM) software Version 7.73, which incorporates consumption 

data from USDA’s Continuing Surveys of Food Intake for Individuals (CSFII), 1989-1992. The 

1989-92 data are based on the reported consumption of more than 10,000 individuals over three 

consecutive days, and in total represent more than 30,000 unique “person days” of data. Foods “as 

consumed” (e.g., apple pie) are linked to raw agricultural commodities and their food forms (e.g., 

apples-cooked/canned or wheat-flour) by recipe translation files internal to the DEEM software. 

Consumption data are averaged for the entire US population and within population subgroups (e.g., 

children one to six years old) for chronic exposure assessment, but are retained as individual 

consumption items for acute exposure assessment.

For chronic exposure and risk assessment, estimates of average residues for 

foods (e.g., orange) or food-forms (e.g., orange-juice) of interest are multiplied by the 

averaged consumption estimate of each food/food-form of each population subgroup. 

Exposure estimates are expressed in mg/kg body weight/day and as a percent of the 

cPAD. 

For acute exposure assessments, individual one-day consumption data are used 

on an individual-by-individual basis. The reported consumption amounts of each food 

item can be multiplied by a residue point estimate and summed to obtain a total daily 

pesticide exposure for a deterministic (Tier 1 or Tier 2) exposure assessment, or 

“matched” in multiple random pairings with residue values and then summed in a 

probabilistic (Tier 3/4) assessment. The resulting distribution of exposures is expressed 

as a percentage of the aPAD on both a user (i.e., those who reported eating relevant 

commodities/food forms) and a per-capita basis.
 25  44

4.2.2.2 Acute Dietary Exposure/Risk Assessment

An acute dietary exposure analysis was conducted for diquat dibromide using the DEEM

software (B. Daiss, D277766, 12/11/01). The acute dietary exposure/risk analysis was conducted 

using a conservative deterministic (Tier I) methodology. The Tier I analysis assumes that; 1) 

residues are present at published tolerances for registered uses and at recommended tolerances for 

proposed new uses, and 2) 100% crop treated (CT) for all commodities with existing and/or 

recommended tolerances. Tier I acute dietary analyses were conducted for the general U.S. 

population and all population subgroups. Based on this analyses, acute dietary risk associated with 

exposure to diquat from existing and proposed uses are below the Agency’s level of concern for 

the general US population and population subgroups. The 95th percentile acute exposure estimates 

were < 100% of the acute Population Adjusted Dose (aPAD). The highest acute exposure ( 

0.0054 mg/kg/day) was in children 1-6 years old (<1% aPAD). The results are presented in Table 

6.

Table 6. Acute Dietary (Food) Exposure Estimate and Percent of Acute RfD at the 95th Percentile - Tier 1 

Exposure Analysis (Assumes 100% Crop Treated and Tolerance Level Residues)

Subgroups 95th Percentile Exposure (mg/kd/day) % aPAD at 95th Percentile Exposure

US Population (total) 0.0039 < 1

All Infants (<1 year old) 0.0035 < 1

Children 1-6 years old 0.0054 < 1

Children 7-12 years old 0.0033 < 1

Females 13-50 years old 0.0032 < 1

Males 13-19 years old 0.0030 < 1

Males 20+ years old 0.0035 < 1

Seniors 55+ years old 0.0023 < 1

4.2.2.3 Chronic Dietary Exposure/Risk Assessment

A chronic dietary exposure analysis was conducted for diquat dibromide using the 

DEEM software. The chronic dietary analysis was conducted using a conservative deterministic 

(Tier I) methodology (i.e., residues present at tolerance levels and 100 %CT). Tier I chronic 

dietary analyses were conducted for the general U.S. population and all population subgroups. 

Based on this analyses, chronic dietary risk associated with exposure to diquat from existing and 

proposed uses are below the Agency’s level of concern for the general US population and 

population subgroups. The chronic exposure estimates were < 100% of the chronic PAD (cPAD) 

with the highest chronic exposure (0.0031 mg/kg/day) occurring in children 1-6 years old (62% 

cPAD). Results are presented in Table 7.
 26  44

Table 7. Chronic Dietary (Food) Exposure Estimate and Percent of Chronic RfD - Tier 1 Exposure Analysis 

(Assumes 100% Crop Treated and Tolerance Level Residues)

Subgroups Mean Exposure (mg/kd/day) % cPAD at Mean Exposure

US Population (total) 0.0019 38

All Infants (<1 year old) 0.0017 33

Children 1-6 years old 0.0031 62

Children 7-12 years old 0.0021 42

Females 13-50 years old 0.0017 34

Males 13-19 years old 0.0018 26

Males 20+ years old 0.0019 38

Seniors 55+ years old 0.0015 31

4.3. Drinking Water Exposure/Risk Pathway

4.3.1. Environmental Fate Assessment

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 and 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. 

4.3.2 Estimated Environmental Concentrations/Monitoring Results

The Environmental Fate and Effects Division (EFED) performed a Tier I drinking water 

assessment for diquat dibromide for both terrestrial uses and aquatic uses (D281199, J. Breithaupt, 

3/5/01). EFED used both computer models and monitoring data to estimate environmental 

concentrations of diquat in surface and ground water. For terrestrial uses, EFED assessed 

preharvest application to potatoes, alfalfa, and clover with aerial and ground equipment and 

application to clover trees, vines, small fruits, and vegetables using directed spray from ground 

equipment. The assessed aquatic uses include application to lakes and flowing streams. 
 27  44

4.3.2.1 Terrestrial Uses

Surface Water

The FQPA Index Reservoir Screening Tool (FIRST) model was used to estimate 

environmental concentrations in drinking water from surface water contaminated by terrestrial use 

of diquat. FIRST is based upon the linked Pesticide Root Zone Model (PRZM) which simulates 

pesticides in field run-off and Exposure Analysis Modeling System (EXAMs) which simulates 

pesticide fate and transport in an aquatic environment. However, where previous PRZM-EXAMs 

models used a standard field pond scenario, FIRST uses an Index Reservoir which is based on 

Shipman City Lake in Illinois ( 13 acres in area, 9 feet deep, and a watershed area of 427 acres). 

In addition, FIRST uses a Percent Cropped Area (PCA) factor which translates to reduction of area 

within the reservoir that is planted to modeled crop. Due to the change from the standard pond to 

Index Reservoir, the physical scenario as well as the treatment of spray drift is different in FIRST. 

FIRST is designed to produce more realistic estimates of pesticides in surface water that is used as 

a source of drinking water. 

FIRST was used to model the following diquat scenarios: trees/vines/small

fruits/vegetables (maximum use rate of 1 lb a.i./A, single application, 87 PCA); potatoes (0.5 lb 

a.i./A, 2 applications, 14 day application interval, 87 PCA); and alfalfa/clover/non-crop (0.5 lb 

a.i./A, 1 application, single application, 87 PCA) . The surface water estimated environmental 

concentrations (EECs) generated by FIRST ranged from 6.3- 13.2 ppb (ug/L) for peak exposure 

and 0.2-0.4 ppb for annual average exposure. 

Groundwater

EFED used the Screening Concentration in Ground Water (SCI-GROW) model to estimate 

diquat concentrations in groundwater contaminated by terrestrial uses. SCI-GROW is a regressionbased model that uses few input parameters: pesticide’s organic carbon partition coefficient (Koc), 

aerobic soil degradation half-life, and product label application rate and frequency (Barrett, 1997). 

It provides a groundwater screening concentration for use in determining potential risk to human 

health from drinking water contaminated with a pesticide. The groundwater concentration is 

estimated based on the maximum application rates in areas where groundwater is exceptionally

vulnerable to contamination. These vulnerable areas are characterized by high rainfall, rapidly

permeable soil, and shallow aquifer. The SCI-GROW model estimated terrestrial use groundwater 

EECs of 0.006 ppb. However, EFED recommends that monitoring data be used in lieu of the SCIGROW results because higher concentrations were observed from monitoring data. 

The sources of available monitoring data include the South Florida Water Management 

District (SFWMD), and potable water modeling studies from the registrant, and monitoring data 

from the EPA Office of Water (OW). The SFWMD data contained a total of 42 samples that were 

taken from April 1992 to November 2000 on approximately a 1-3 month interval. For diquat, the 

only detection observed in surface water was 0.0045 ppm in 1994. Further monitoring beyond 
 28  44

1994 has not shown any detections in surface water. Also in the SFWMD, diquat was detected in 9

sediment samples from canals with a maximum concentration of 3.1 ppm (LOD of 2.5 ppm, Miles 

and Pfeuffer, Pesticides in Canals of South Florida, Arch. Environ. Contam. Toxicol. 32:337-345, 

1997). In the potable water modeling studies, highly variable estimates of water concentrations 

have been observed. The modeling concentrations at reservoir pumps ranged from non-detections 

(LOD of 0.003 ppm) to 0.26 ppm. These modeling estimates were not used in this assessment 

because of available monitoring data obtained by OW. OW has monitored for diquat at intake 

pumps at drinking water utilities that use surface water and ground water. Data from eight states in 

the years 1993-1997 were included in the report. In these eight states, 0.06 percent of combined 

surface water and ground water systems reported exceedences of the 0.02 ppm (mg/L) Maximum 

Contaminate level (MCL) set by OW, resulting in a population exceedence of 0.27 % (Occurrence 

of Regulated Contaminants in Drinking Water: First Stage Occurrence and Exposure Report for 

Six-Year Regulatory Review, Working Draft 5/12/2000). Based on municipal monitoring data, 

EFED recommends use of the MCL of 0.02 ppm (20 ppb) for both peak and average terrestrial use 

EECs for groundwater. 

4.3.2.2 Aquatic Uses

EFED also relied on monitoring data to estimate surface water and ground water 

concentrations from aquatic uses of diquat. For the aquatic use, EFED also included use 

information from the U.S. Corp of Engineers and the states of Florida, Minnesota, and Michigan. 

For aquatic use, EFED recommends use of the MCL of 0.02 ppm (20 ppb) for both peak and 

annual average EECs. EFED recommends use of the same annual average EECs for both surface 

and groundwater contaminated by aquatic uses of diquat because diquat is used near wells located 

next to lakes and ponds resulting in interaction between surface water and ground water. EFED 

notes that, while concentrations in excess of 20 ppb in private wells cannot be ruled out, they are 

unlikely because of the tendency of diquat to sorb nearly irreversably to soil and sediment. 

EECs for surface and groundwater terrestrial and aquatic uses are provided in the Tables 8 and 9 

respectively.

Table 8. FIRST EEC’s for Diquat for Drinking Water Assessment from Surface Water

Type of Use Use Site Peak (ppb) Average Annual (ppb)

Terrestrial Trees, vines, small fruits, vegetables 13.2 0.4

Alfalfa, Clover 6.3 0.2

Non-Crop (fallow land) 6.6 0.2

Potatoes 12.7 0.4

Aquatic Ditches, reservoirs, and rivers 20120

1 MCL from Office of Water
 29  44

Table 9. Monitoring EEC’s for Diquat for Drinking Water Assessment from Ground Water

Type of Use Use Site Peak (ppb) Average Annual (ppb)

Terrestrial Trees, vines, small fruits, vegetables, alfalfa, clover, 

non-crop (fallow land), and potatoes

20 20

Aquatic Ditches, reservoirs, and rivers 20 20

4.4 Residential Exposure/Risk Assessment

A regulatory review of residential exposure to diquat dibromide was conducted for this 

TRED because there is potential exposure to non-occupational (residential) handlers (mixers, 

loaders, applicators, etc.) during handling and application of diquat and/or to persons entering 

treated sites after its application (T. Brennan, 12/14/01, D279507). Only short-term exposures are 

expected/assessed for residential exposure scenarios.

4.4.1 Home Uses

4.4.1.1 Handler

Handler Exposure Scenarios

Diquat dibromide can be applied to turf and backyard ponds for general weed control and 

can be used in and around home & garden sites for weed control and landscape uses by residential 

handlers. Diquat dibromide is applied to residential turf grass at application rates ranging from 

0.25 to 0.5 lb ai/acre. Therefore, for this assessment both low end and high end MOEs were 

assessed based on the range of application rates. Diquat dibromide is formulated for residential 

uses both as a Liquid Ready to Use, and as a Soluble Concentrate/Liquid that can be mixed with 

water and then applied with a low pressure handwand or backpack sprayer. This TRED estimates

exposure and risk for four residential handler scenarios: 

1) Mixing, loading, and applying with a low pressure handwand - This residential handler 

scenario estimates exposure and risk to a mixer, loader, applicator applying diquat 

dibromide with a low pressure handwand to control weeds in and around lawns, gardens, 

around buildings, driveways, fence lines and other such edge areas. The dermal and 

inhalation unit exposures for this scenario were obtained from the Outdoor Residential 

Exposure Task Force (ORETF) chemical handler exposure studies.

2) Mixing, loading, applying with a backpack sprayer - This scenario estimates exposure 

and risk to a mixer, loader, applicator applying diquat dibromide with a backpack sprayer to 

control residential weeds in edge areas.
 30  44

3) Applying with an aerosol sprayer - This scenario estimates exposure and risk to an 

applicator applying diquat with an aerosol spray can to control residential weeds in edge 

areas. 

4) Applying with a trigger pump sprayer - This scenario estimates exposure and risk to an 

applicator applying diquat dibromide with an trigger pump sprayer to control residential 

weeds. The dermal and inhalation unit exposures for this scenario were obtained from a 

carbaryl Occupational and Residential Exposure Task Force (ORETF) study on ready-touse insect sprayer application to home garden vegetables.

The handler assessment was developed using standard residential application techniques 

and PHED unit exposure data. It is the policy of the HED to use data from the Pesticide Handlers 

Exposure Database (PHED) Version 1.1 to assess handler exposures for regulatory actions when 

chemical-specific monitoring data are not available. PHED was designed by a task force of 

representatives from the US. EPA, Health Canada, the California Department of Pesticide 

Regulation, and members of the American Crop Protection Association. PHED is a software 

system consisting of two parts; 1) a database of measured exposure values for workers involved in 

the handling of pesticides under actual field conditions, and 2) a set of computer algorithms used to 

subset and statistically summarize the selected data. Currently, the database contains values for 

over 1,700 monitored individuals (i.e., replicates). For the handler scenarios female adult 

applicators were assessed for dermal exposures because the dermal toxicity endpoint was based on 

developmental toxicity effects. A complete summary of the handler dermal exposure and risk 

calculations, critical assumptions, and results is provided in Table 10. Handler exposure 

assumptions are summarized below.

Handler Exposure Assumptions

The following assumptions were made in the exposure calculations:

· Average body weight of an adult handler is 70 kg/day.

· Application rates range from a low-end rate 0.009 to a high-end 0.018 lb ai/gallon of 

sprayer.

· Backpack sprayers and low pressure handwands were applied at a rate of 5 gallons per 

day. Aerosol cans and triggers sprayers were applied at a rate of 0.125 gallons per day.

· No protective clothing was factored into the assessment for these residential handler 

exposure/risk scenarios. Clothing assumptions include short pants, short-sleeved shirt, 

and no gloves.

· Exposure frequency - The residential handlers are expected to have a short-term 

exposure duration (less than 30 days).

Handler Exposure and Risk Estimates
 31  44

A target MOE of 100 for the dermal and inhalation routes are considered adequate for the 

handler risk assessment. Results of handler exposure assessment are presented in Table 10 and are 

summarized below. 

1) Low pressure handwand scenario - The adult applicator dermal MOEs were 670 for the 

low end scenario and 330 for the high end scenario. The inhalation MOEs were 8,800 for 

the low end scenario and 4,400 for the high end scenario. 

2) Backpack sprayer scenario - The adult applicator dermal MOEs were 7,500 for the low 

end scenario and 3,700 for the high end scenario. The inhalation MOEs were 1,400 for the 

low end scenario and 720 for the high end scenario.

3) Aerosol can scenario - The adult applicator dermal MOEs were 6,900 for the low end 

scenario, and 3,500 for the high end scenario. The inhalation MOEs were 720 for the low 

end scenario, and 360 for the high end scenario.

4) Trigger pump spray scenario - The adult applicator dermal MOEs were 24,390 for the 

low end scenario, and 14,000 for the high end scenario. The inhalation MOEs were > 

24,000,000 for the low end scenario, and > 12,000,000 for the high end scenario.

Table 10: Diquat Dibromide Residential Handler Short Term Exposure and Risk Assessment

Exposure Scenario 

(Scenario #)

Dermal 

Unit 

Exposure 

(mg/lb 

ai)

Inhalation 

Unit 

Exposure 

 (ug/lb 

ai)

Crop

(rate)

Applicati

on Rate

(lb ai per 

gal)

Amount 

Treated 

(gal per 

day) 

Dermal 

Absorbed 

Dose c

(mg/kg/d)

Dermal 

MOE d

Inhalation 

Dose e

(mg/kg/d)

Inhalation 

MOE f

Mixer/Loader/App

Mixing/Loading/Applying 

Liquids for Low Pressure 

Handwand application (1)a

100 30 high end 0.018 5 0.003 330 0.0000055 4400

Mixing/Loading/Applying 

Liquids for Low Pressure 

Handwand application (2)a

100 30 low end 0.009 5 0.0015 670 0.0000028 8800

Mixing/Loading/Applying 

Liquids for Backpack sprayer 

application (3)b

5.1 30 high end 0.018 5 0.00027 3700 0.000038 720

Mixing/Loading/Applying 

Liquids for Backpack sprayer 

application (4)b

5.1 30 low end 0.009 5 0.00013 7500 0.000019 1400

Applicator

Aerosol can application (5)b220 2400 high end 0.018 0.125 0.00029 3500 0.000077 360

Aerosol can application (6)b220 2400 low end 0.009 0.125 0.00014 6900 0.000039 720

Trigger Sprayer (7)a53 0.067 high end 0.018 0.125 0.00007 14000 2E-09 12000000

Trigger Sprayer (8)a53 0.067 low end 0.009 0.125 0.000041 24390 1E-09 24000000

Footnotes:

a Baseline dermal and inhalation exposure derived from the ORETF chemical handler exposure studies.

b Baseline dermal unit exposure represents short pants, short-sleeved shirt, no gloves, open mixing/loading, open cab/tractor. Values from PHED 

V1.1. Baseline inhalation unit exposure represents no respirator. Values from PHED V1.1.

c Dermal daily dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/acre) x amount handled per day (acres) / bw (60 kg).

d Dermal MOE = NOAEL (1 mg/kg) / [daily dose (mg/kg/day) x dermal absorption factor (4.1%)].
 32  44

e inhalation daily dose (mg/kg/day) = inhalation unit exposure (μg/lb ai) x application rate (lb ai/acre) x amount handled per day (acres) x 

conversion factor (1 mg/1,000 μg) / body weight (70 kg). 

f Inhalation MOE = NOAEL (0.1 ug/L) / daily dose (mg/kg/day). 

4.4.1.2 Postapplication

Diquat dibromide is used on dormant turf grass for weed control. Diquat dibromide will 

kill all types of vegetation and can be used to kill turf grass. Based on this and a review the labels, 

HED conducted a lawn post-application analysis. Diquat dibromide is specifically labeled to be 

applied on dormant Bermuda and zoysia grass. Therefore re-entry must be addressed. Only shortterm exposures (1 to 30 day period of exposure) are assessed because residents can have postapplication exposure to treated lawns in the initial hours and days following treatment. Diquat 

dibromide is applied to residential turf grass at application rates ranging from 0.25 to 0.5 lb ai/acre. 

Therefore, for this assessment both low end and high end MOEs were assessed based on the range 

of application rates. 

Postapplication Exposure Scenarios

Four post-application scenarios were assessed:

1) Dermal exposure to treated turf grass - adults and children - This post-application 

scenario estimates the dermal exposures and risk to adults and toddlers from dermal contact 

with turf treated with diquat dibromide. This scenario assumes that diquat dibromide 

residues are transferred to the skin of adults/toddlers who enter treated yards for recreation, 

yard work, or other homeowner activities. 

2) Toddler ingestion of treated turf grass via object-to-mouth activities - This postapplication scenario estimates doses among toddlers from incidental ingestion of residential 

turf grass that has been previously treated with pesticides. This scenario assumes that turf 

is ingested (or just mouthed) by toddlers who play in the treated areas. 

3) Toddler ingestion of residue via hand-to-mouth activity while on treated turf grass - This 

post-application scenario estimates potential ingestion of pesticide residues from previously

treated turf. This scenario assumes that pesticide residues are transferred to the skin of 

toddlers playing on treated yards and are subsequently ingested as a result of hand-to-mouth 

transfer.

4) Toddler ingestion of soil from treated area - This post-application scenario estimates 

doses among toddlers from incidental ingestion of soil containing pesticide residues. This 

scenario assumes that pesticide residues in soil are ingested by toddlers who play in treated 

areas. 

The turf, post-application assessments were developed using the Residential SOP guidance. 

The exposure and risk calculations, critical assumptions, and results are provided in Table 11 for 

postapplication dermal scenarios and in Table 12 for postapplication incidental oral exposure. 

Post-application exposure assumptions are summarized below.

Postapplication Exposure Assumptions
 33  44

The following assumptions were made in the dermal postapplication exposure calculations:

· Application rates range from a low-end rate of 0.25 to a high-end rate of 0.50 lbs ai/acre.

· Turf transferable residue is equal to 5 % of the application rate.

· Turf transfer coefficient is 14,500 cm2/hr for adult and 5,200 cm2/hr for children.

· Exposure duration is 2 hours for exposure to residential lawns, and 4 hours for exposure 

to golf course turf. 

· Body weight is 70 kg for adults, and 15 kg for toddlers.

The following assumptions were made in the oral postapplication exposure calculations:

· Application rates range from a low-end rate of 0.25 to a high-end rate of 0.50 lbs ai/acre.

· Hand and object transfer efficiency is equal to 5 % of the application rate available for 

transfer from treated turf to wet hands and objects.

· Surface portion of hand put in mouth is 20 cm2.

· Hand-to-mouth exposure frequency is 20/times per hour.

· Body weight is 15 kg for toddlers.

· Exposure time 2 hours.

· Saliva extract factor (for hand-to-mouth only) is 50 percent.

Postapplication Exposure and Risk Estimates

A target MOE of 100 for both the dermal and incidental oral routes is considered adequate 

for the postapplication risk assessment. Results of post application assessment are presented in 

Tables 11 and 12 and are summarized below. 

1) Dermal exposure to treated turf grass - adults and children - The adult MOEs for reentering treated lawns were not a risk concern with a low end MOE of 480, and a high end 

MOE of 220. The toddler MOEs for this scenario were also not a risk concern with a low 

end MOE of 270 and a high end MOE of 130. 

2) Toddler ingestion of treated turf grass via object-to-mouth activities - The toddler MOEs 

for ingesting (or mouthing) of treated turf grass were not a risk concern with the low end 

MOE of 1,110, and a high end MOE of 560.
 34  44

3) Toddler ingestion of residue via hand-to-mouth activity while on treated turf grass - The 

toddler MOEs from incidental exposure arising from hand-to-mouth transfer of diquat 

dibromide were not a risk concern with the low end scenario MOE of 290 and the high end 

scenario MOE of 145.

4) Toddler ingestion of soil from treated area - The toddler MOEs for ingesting (or 

mouthing) of treated soil were not a risk of concern with the low end MOE of 83,300, and a 

high end MOE of 41,670.

Table 11. Dermal Post-application Risks to Toddlers and Adults When Reentering Treated Lawns on Day 0 after 

Sprays have Dried

Scenario Range

Finder1

Application

Rate

(lb ai/acre)

Fraction

of Residue

Retained

Transfer 

Coefficient

(cm2/hr)

Exposure 

Duration

(hours)

Body

Wt

(kg)

Daily 

Dermal 

Dose2(mg/kg/d)

Dermal 

MOE3

Toddler Low End 0.25 0.05 5,200 2 15 0.09 270

High End 0.5 0.05 5,200 2 15 0.19 130

Adult Low End 0.25 0.05 14,500 2 70 0.051 480

High End 0.5 0.05 14,500 2 70 0.11 220

1 Low end ranges are derived from the lowest labeled application rates, while the high end ranges are derived from the highest labeled rates 

EPA Reg. No. 10182-404. These application rates represent broadcast application to dormant, established turf grass. 

2 Dermal potential dose rates are calculated as follows:

PDRt = DFRt * CF1 * Tc * ET

where:

PDRt = potential dose rate on day “t” (mg/day).

DFRt = dislodgeable foliar residue on day “t” (ug/cm2).

CF1 = weight unit conversion factor to convert ug units in the DFR to mg for the daily dose (0.001 mg/ug)

Tc = transfer coefficient (cm2/hr).

ET = exposure time (hr/day).

and

DFRt + AR * F * (1-D)t * CF2 * CF3 

where:

AR = application rate (lbs ai/ft2or lb ai/acre).

F = fraction of ai retained on foliage (unitless).

D = fraction of residue that dissipates daily (unitless).

t = post-application day on which exposure is being assessed.

CF2 = weight unit conversion factor to convert the lbs ai in the application rate to ug for the DFR value (4.54E8 ug/lb)

CF3 = area unit conversion factor to convert the surface area units (ft2) in the application rate to cm2for the DFR value 

(1.08E-3 ft2/cm2or 24.7E-9 acre/cm2

if the application rate is per acre)

3

Post-application Dermal MOE = Oral NOAEL (1 mg/kg/day)/[Daily Dermal Dose (mg/kg/day) x Dermal Absorption Value (4.1%)]. 

MOEs are reported to two significant figures.

Table 12. Oral Post-application Risks to Toddlers from Oral Exposures When Reentering Treated Lawns

Type of

Exposure

Range

Finder1

Application

Rate

(lb ai/acre)

Fraction

of Residue

Available 

on Foliage

Ingestion Rate or 

Other Assumptions

Saliva

Extraction 

Factor 

Exposure 

Duration

(hours)

Body 

Wt

(kg)

Daily 

Oral 

Dose2

(mg/kg/d)

MOE 3

Exposure to Low End 0.25 0.20 NA 2 15 0.0009 1,110
 35  44

Table 12. Oral Post-application Risks to Toddlers from Oral Exposures When Reentering Treated Lawns

Type of

Exposure

Range

Finder1

Application

Rate

(lb ai/acre)

Fraction

of Residue

Available 

on Foliage

Ingestion Rate or 

Other Assumptions

Saliva

Extraction 

Factor 

Exposure 

Duration

(hours)

Body 

Wt

(kg)

Daily 

Oral 

Dose2

(mg/kg/d)

MOE 3

Treated Turf Grass 

via object-to-mouth 

activities5

High End 0.5 25 cm2

/day ingestion 0.0018 560

Hand-to-Mouth 

Activity While on 

Treated Turf Grass

Low End 0.25 0.05 20 hand-to-mouth 

events per hour;

20 cm2/day exposed 

surface area per event

50% 0.0035 290

High End 0.5 0.007 145

Soil6 Low End 0.25 NA 100 mg/day ingestion NA 0.000012 83,330

High End 0.5 0.000024 41,670

1 Low end ranges are derived from the lowest labeled application rates, while the high end ranges are derived from the highest labeled rates 

EPA Reg. No. 10182-404. These application rates represent broadcast application to dormant, established turf grass. 

2 Object-to-mouth exposure to treated turf grass potential dose rates from ingestion are calculated as follows:

PDRt = GRt * IgR * CF1

where:

PDRt = potential dose rate on day “t” (mg/day)

GRt = grass (and plant matter) residue on day “t” (ug/cm2)

IgR = ingestion rate of grass (cm2/day)

CF1 = weight unit conversion factor to convert ug units in the DFR to mg for the daily dose (0.001 mg/ug)

Hand-to-mouth potential dose rates from ingestion are calculated as follows:

PDRt = DFRt * SA * FQ * SEF * ET * CF1

where:

PDRt = potential dose rate on day “t” (mg/day).

DFRt = dislodgeable foliar residue on day “t” (ug/cm2turf).

SA = surface area of the hands (cm2/event).

SEF = saliva extraction factor (%)

FQ = frequency of hand-to-mouth activity (events/hr).

ET = exposure time (hr/day).

CF1 = weight unit conversion factor to convert ug units in the DFR value to mg for the daily exposure (0.001 mg/ug)

Ingestion of soil from treated area potential dose rates from ingestion are calculated as follows:

PDRt = SRt * Ing * CF1

where:

PDRt = potential dose rate on day ‘t” (mg/day)

SRt = soil residues on day “t” (ug/g)

IgR = ingestion rate of soil (mg/day)

CF1 = weight unit conversion factor to convert ug units in the residues on the soil to g for the daily dose (1.0E-6 g/ug) 

3

Postapplication oral MOE = Oral NOAEL(1 mg/kg/day)/Daily Oral Dose(mg/kg/day). Oral NOAEL determined from a rabbit developmental study. 

MOEs are reported to two significant figures; an acceptable MOE is at least 100. 

Aggregate Post-Application Exposure and Risk Estimate

The short term aggregate post-application risk is the estimated risk associated with 

combined risks from the short term dermal and oral post-application exposures. Given the 

observed effects at the recommended NOAELs for oral and dermal pathways, HED believes that 

risk from these exposure routes can be reasonably added. The inhalation risks are not aggregated 

because the NOAEL for this exposure pathway is based on a distinct target organ effect. 

Aggregate post-application risk is estimated for the child exposure scenario only since the child 
 36  44

may be exposed via both oral and dermal pathways while the adult exposure is from the dermal 

route only. The short term aggregate MOE for the child is calculated by adding exposure 

estimates from the oral and dermal pathways using the formula presented below. The child 

aggregate risk combines the highest exposures from the post-application scenarios (i.e., high-end 

oral and dermal post-application reentry exposure). The calculated short-term aggregate MOE is 

presented in Table 13. The short-term aggregate post-application MOE for the high-end exposure 

scenario for 1-6 year old children is 70. The residential aggregate risk combines screening level 

risk estimates from individual exposure pathways and should be viewed as a highly conservative 

estimate which is certain to over-estimate risk. The estimated risk from the individual pathways is 

based on high-end assumptions, i.e., highest application rates, child reentry/play on the day of 

treatment, and a high-end turf transferable residue factor of 5%. In addition, based on a human 

dermal absorption study cited by the registrant which shows dermal absorption of 0.3%, use of a 

4.1% dermal absorption factor is likely to result in a further overestimation of risk. A refined 

analysis would result in lower exposure estimates and higher MOEs.

MOE Post-Application CHILD = 1 

 1 + 1 

 MOEDERMAL MOEORAL

where:

MOEDERMAL = Short Term Dermal NOAEL (mg/kg/day)  (Short Term Dermal Exposure (mg/kg/day) x 

Dermal Absorption Factor)

MOEORAL = Short Term Oral NOAEL (mg/kg/day)  Short Term Oral Exposure (mg/kg/day)

Table 13. Short Term Aggregate Post-Application Risk to Child

Populatio

n

Subgroup

Short Term 

Oral 

NOAEL

mg/kg/d

Short Term 

Dermal 

NOAEL

mg/kg/d

Short Term Dermal 

Re-entry Exposure 

mg/kg/d1

Short Term Oral 

- Hand to Mouth -

Exposure

mg/kg/d

Oral MOE Dermal 

MOE

PostApplication 

Aggregate 

MOE

Child 1-6 1 1 0.0078 0.007 145 130 70

1

Includes Dermal Absorption Factor of 4.1% (0.19 mg/kg/d x 0.041 = 0.0078)

4.4.2 Recreational

Two recreational post-application exposure scenarios were assessed:

1) Recreational golfer exposure from playing on treated turf grass (adults) - This postapplication scenario estimates dermal exposures and risk to adult golfers from dermal 

contact with turf grass on golf courses that has been previously treated with diquat 

dibromide. The scenario assumes that a golfer re-enters the course after diquat dibromide 

sprays have dried and then play a four hour round of golf.

2) Swimming exposure to treated ponds and lakes - This post-application scenario 

estimates dermal exposures and risk to adult and 7-10 year old swimmers who re-enter 

treated ponds and lakes. Several of the diquat dibromide labels intended for aquatic weed 
 37  44

control uses have swimming re-entry intervals of 0 days (example: EPA Reg. No. 10182-

404).

The exposure and risk calculations, critical assumptions, and results for the recreational 

golfer exposure scenarios are provided in Table 14. Exposure assumptions for the golfer scenario 

are summarized below.

Recreational Golfer Exposure Assumptions

The following assumptions were made in the dermal exposure calculations for recreational 

golfer exposure:

· Application rates range from a low-end rate of 0.25 to a high-end rate of 0.50 lbs ai/acre.

· Turf transferable residue is equal to 5 % of the application rate.

· Turf transfer coefficient is 14,500 cm2/hr for adult

· Exposure duration 4 hours for exposure to golf course turf. 

· Body weight is 70 kg for adults

Table 14. Dermal Post-application Risks Adults When Reentering Golf Courses on Day 0 after Sprays have Dried

Scenario Range

Finder1

Application

Rate

(lb ai/acre)

Fraction

of Residue

Retained

Transfer 

Coefficient

(cm2/hr)

Exposure 

Duration

(hours)

Body

Wt

(kg)

Daily 

Dermal 

Dose2(mg/kg/d)

Dermal 

MOE3

Adult 

Golfer

Low End 0.25 0.05 500 4 70 0.0034 7,100

High End 0.5 0.05 500 4 70 0.0077 3,200

1 Golfer durations are assumed to be 4 hours for an 18-hole round of golf.

2 Dermal potential dose rates are calculated as follows: PDRt = DFRt * CF1 * Tc * ET

3

Post-application Dermal MOE = Oral NOAEL (1 mg/kg/day)/[Daily Dermal Dose (mg/kg/day) x Dermal Absorption Value (4.1%)]. MOEs are 

reported to two significant figures.

Swimmer Exposure Assumptions

In order to assess potential exposures to swimmers who re-enter treated ponds and lakes, 

HED used the Swimmer Exposure Assessment Model (SWIMODEL). The SWIMODEL was 

developed for estimating the human exposure doses to the pesticides and toxic pollutants in 

swimming pools. This model is a modification of a study used by J. A. Beech (1980) for 

estimating exposure to Trihalomethanes (THM) in swimming pools. Clearly swimming in ponds 

and lakes is different than pools in many ways; however, the basic exposure to chemicals in the 

water column are similar enough to warrant using this model for this TRED. 
 38  44

The model is based on exposure routes and age-specific contact factors, exposure duration 

and frequency, chemical/physical properties of the pollutant, and pollutant concentration, total 

exposure doses can be approximated by the model. For this TRED child (age 7-10) and adult 

swimmers were modeled. One diquat dibromide concentration in the lake was modeled for this

analysis: 20 ppb – the maximum contaminant goal which was reported by EFED as a high end, 

monitoring data endpoint. The exposure and risk calculations, critical assumptions, and results for 

the swimmer scenario are provided in Table 15.

Table 15. Child and Adult Exposure and Risk to Swimming in Treated Lakes on Day 0

Exposed 

Population

Concentration 

in Lake (ppm)1

Total Exposure 

(mg/event)2

Body Weight 

(kg)3

Total Dose 

(mg/kg/day)4

MOE5

Child (age 7-10) 20 0.062 37.8 0.0016 630

Adult 20 0.0087 84.4 0.0001 10,000

1

 The concentration in the lake was run at 20 ppb (the maximum contaminant goal reported by EFED as a high end, 

monitoring data endpoint).

2 Total exposure is a combination of exposures via the following routes: oral, dermal, buccal/sublingual, orbital/nasal, 

aural, and inhalation.

3 Body weights represent the 90% for the population being modeled.

4 Total dose (mg/kg/day) = Total exposure (mg/event) / body weight (kg)

5 MOE = Oral NOAEL 1 mg/kg/day / Total dose (mg/kg/day)

Recreational Exposure and Risk Estimates

A target MOE of 100 for both the dermal and incidental oral routes is considered adequate 

for the recreational risk assessment. Results of the recreational exposure assessment are presented 

in Tables 14 and 15 and are summarized below.

1) The MOEs for an adult playing a round of golf on a treated golf course were not a risk 

concern. MOEs ranged from 7,100 for the low-end exposure scenario to 3,200 for the highend scenario.

2) Estimated MOEs were not a risk of concern for child or adult swimmers. MOEs for 

children age 7-10 ranged from 630 to 180. MOEs for adults ranged from 10,000 to 770.

4.5 Incident Reports 

The vast majority of incident reports for diquat fall into one of two categories: (1) people 

exposed while handling the product for its intended purpose; and, (2) people who drank the 

pesticide either by accident or on purpose (i.e., in order to harm themselves) (M. Spann and J. 

Blondell, 10/15/01, D278482). According to a several of pesticide incident sources, diquat 

dibromide ranked relatively high on the list of pesticides with reported incidents. Detailed 

descriptions of 112 cases submitted to the California Pesticide Illness Surveillance Program (1982-
 39  44

1999) were reviewed. In 76 of these cases, diquat was used alone or was judged to be responsible 

for the health effects. Only cases with a definite, probable or possible relationship were reviewed. 

Diquat ranked 50th as a cause of systemic poisoning in California based on data for 1982 through 

1999. Similarly, on the list of the top 200 chemicals for which National Pesticide 

Telecommunications Network received calls from 1984-1991 inclusively, diquat was ranked 54th

with 74 incidents in humans reported. From the review of California data, it appears that a majority

of cases involved systemic, eye, and skin illnesses such as eye irritation/pain, skin rash, chemical 

burns, chemical conjunctivitis, nausea, and vomiting. Poison Control Center data tend to support 

the California data, eye irritation/pain, erythema, rash, skin itching, corneal abrasion, lacrimation, 

dyspnea, coughing, and choking were the most common effects reported due to exposure. Oral 

exposure to even modest amounts can lead to severe poisoning and even death.

4.5.1 Residential Handler Incidents

Of all the handler incident reports, “applicator” was associated with more exposures than 

any other category. These illnesses included symptoms of burning and itching eyes, dizziness, 

nausea, dyspnea, rashes, chemical conjunctivitis, vomiting, dermatitis, and chemical burns. 

4.5.2 Postapplication and Recreational Incidents

Not many cases of post-application exposures have been reported, however there was one 

incident involving swimmers. In this case, two boys swam in a lake that had been treated with 

diquat three days prior to the activity. Both boys developed a rash, one much more severe than the 

other. The nine year old boy with the more serious rash was treated by a physician while the other 

boy was treated at home. No information was provided on levels of diquat in the treated lake.

5.0 AGGREGATE RISK ASSESSMENT AND RISK CHARACTERIZATION

The aggregate risk assessment integrates the assessments conducted for dietary and 

residential exposure. Since there is potential for concurrent exposure via the food, water and 

residential pathways, the combined exposures are estimated using the methodology described 

below and are compared with monitoring-based estimates of drinking water contamination 

determined by EFED. All routes of diquat dibromide exposure have been considered. Aggregate 

exposure pathways for adults include dietary, drinking water, and dermal and inhalation exposures 

from application and post-application activities. Aggregate exposure pathways for children include 

dietary, drinking water, and dermal and oral exposures from post-application exposure. 

5.1 Acute Aggregate Risk Assessment

The acute aggregate risk is the estimated risk associated with combined acute food and 

drinking water exposure. The acute aggregate MOE is calculated by adding acute dietary exposure 

estimates with drinking water levels obtained from monitoring data using the formula presented 

below. The target MOE for acute aggregate risk is 100. The calculated acute aggregate
 40  44

MOEs are presented in Table 16. Acute aggregate risk MOEs are below EPA’s level of concern 

(i.e., to 100) for all population subgroups. Since the estimated risk from the individual pathways 

are considered to be screening level, the aggregates should be considered as a highly conservative 

estimate of risk. 

MOE Aggregateacute = 1 

 1 + 1 

 MOEFOOD MOEWATER

where:

MOEFOOD = Acute Dietary NOAEL (mg/kg/day)  Acute Dietary Exposure (mg/kg/day)

MOEWATER= Acute Dietary NOAEL (mg/kg/day)  Acute Water Exposure (mg/kg/day)

and: 

Acute Water Exposure = Acute Water EEC (mg/L) x Drinking Water Consumption (L/day) 

(mg/kg/d) Body Weight (kg)

Table 16. Acute Aggregate Risk

Population Subgroup Acute 

Dietary 

NOAEL 

(mg/kg/day)

Acute 

Dietary 

Exposure

(mg/kg/day)

Acute Water

EEC

(mg/L)

DW 

Consumption 

(L/day)

Body

Weight

(kg)

Acute Water 

Exposure

(mg/kg/day)

Acute

Aggregate 

MOE

US Population (total) 75 0.0039 0.02 2 70 0.00057 16773

All Infants (<1 year old) 75 0.0035 0.02 1 10 0.002 13636

Children 1-6 years old 75 0.0054 0.02 1 10 0.002 10135

Children 7-12 years old 75 0.0033 0.02 1 10 0.002 14151

Females 13-50 years old 75 0.0032 0.02 2 60 0.00067 19397

Males 13-19 years old 75 0.0030 0.02 2 70 0.00057 21000

Males 20+ years old 75 0.0035 0.02 2 70 0.00057 18421

Seniors 55+ years old 75 0.0023 0.02 2 70 0.00057 26119

5.2 Short-Term Aggregate Risk Assessment

The short term aggregate risk is the estimated risk associated with combined risks from the 

following pathways: chronic dietary intake, average annual drinking water exposures, and short 

term dermal and oral (if applicable) exposures. Given the observed effects at the recommended 

NOAELs for each of these pathways, HED believes that risk from these exposure routes can be 

reasonably added. The inhalation risks are not aggregated because the NOAEL for this exposure 

pathway is based on a distinct target organ effect. The short term aggregate MOE is calculated by

adding exposure estimates from each of these pathways using the formula presented below. The 

adult aggregate risk combines the highest exposures from the various application and postapplication scenarios (i.e., high-end, low pressure handwand applicator exposure, and high-end 
 41  44

adult reentry exposure). Likewise, the highest dermal and oral exposures from the assessed 

scenarios are added for the estimated child risk aggregate. The calculated short-term aggregate 

MOEs are presented in Table 14. The short term aggregate MOE for the high-end exposure 

scenario for the adult applicator is 100. The short-term aggregate MOE for the high-end toddler 

exposure scenario is 55. 

The short-term aggregate risk combines screening level risk estimates from individual 

exposure pathways and should be viewed as a highly conservative estimate, certain to overestimate risk. A refined analysis would result in lower exposure estimates and higher MOEs. 

Possible refinements include: 1) revising the dietary assessment to account for actual percent crop 

treated (i.e., no use involves 100% crop treated; most involve <1% CT) and to reflect residues 

based on field trial data, which are generally much lower than tolerance levels; 2) revising 

estimated environmental concentrations in drinking water sources to reflect lower concentrations in 

a sizeable majority of monitoring samples (i.e., monitoring data from 1993-1997 showed an MCL

exceedence rate of < 1%); and 3) refining the residential exposure scenarios to include more 

plausible assumptions regarding a) the use of protective clothing for applicators (i.e., no protective 

clothing was factored into assessments of residential exposure), b) application rates (i.e., highest 

rates are assumed), c) day of reentry (i.e., children and adults are assumed to reenter and work/play

on the lawn on the day of treatment), d) turf transferable residue (i.e., TTR is assumed to be 5% of 

the application rate - a high-end assumption), and e) dermal absorption factor (i.e., dermal 

absorption is assumed to be 4.1% based on a rat study; a human dermal absorption study cited by

the registrant estimates dermal absorption to be about 0.3% (Feldman RJ and Maibach HI, 

“Percutaneous penetration of some pesticides and herbicides in man” Tox. Appl. Pharm. 28 126-

132, 1974)). 

MOE Aggregate SHORT TERM = 1 

 1 + 1 + 1 + 1 

 MOEFOOD MOEWATER MOEDERMAL MOEORAL* * If applicable

where:

MOEFOOD = Short Term Oral NOAEL (mg/kg/day)  Chronic Dietary Exposure (mg/kg/day)

MOEWATER = Short Term Oral NOAEL (mg/kg/day)  Chronic Water Exposure (mg/kg/day)

MOEDERMAL = Short Term Dermal NOAEL (mg/kg/day)  (Short Term Dermal Exposure (mg/kg/day) x 

Dermal Absorption Factor)

MOEORAL = Short Term Oral NOAEL (mg/kg/day)  Short Term Oral Exposure (mg/kg/day)

and: 

Water Exposure = Chronic Water EEC (mg/L) x Drinking Water Consumption (L/day) 

 (mg/kg/d) Body Weight (kg)

Table 17. Short Term Aggregate Risk

Population

Subgroup

Short Term 

Oral 

NOAEL

mg/kg/d

Chronic 

Dietary

Exposure

mg/kg/d

Annual 

Avg Water 

Exposure

mg/kg/d

Short Term 

Dermal 

NOAEL

mg/kg/d

Short Term Dermal 

Exposure -

Handwand Applicator

mg/kg/d1

Short Term 

Dermal 

Exposure Reentry

mg/kg/d1

Short Term Oral 

- Hand to Mouth -

Exposure

mg/kg/d

Short 

Term 

Aggregate 

MOE

Male 20+ 1 0.0018 0.00057 1 0.003 0.0045 NA 100

Child 1-6 1 0.0031 0.002 1 NA 0.0078 0.007 55

1

Includes Dermal Absorption Factor of 4.1% (0.11 mg/kg/d x 0.041 = 0.0045; 0.19 mg/kg/d x 0.041 = 0.0078)
 42  44

5.3 Chronic Aggregate Risk Assessment

The chronic aggregate risk is the estimated risk associated with combined chronic food and 

drinking water exposure. The chronic aggregate MOE is calculated by adding chronic dietary

exposures and estimated average annual drinking water concentrations using the formula presented 

below. The target MOE for chronic aggregate risk is 100. The calculated chronic aggregate MOEs 

are presented in Table 18. Chronic aggregate risk MOEs are below EPA’s level of concern (i.e., 

to 100) for all population subgroups. Again, since the aggregate combines screening level risks 

from individual exposure pathways, the chronic aggregate risk estimate is highly conservative.

MOE AggregateCHRONIC = 1 

 1 + 1 

 MOEFOOD MOEWATER

where:

MOEFOOD = Chronic Dietary NOAEL (mg/kg/day)  Chronic Dietary Exposure (mg/kg/day)

MOEWATER= Chronic Dietary NOAEL (mg/kg/day)  Chronic Water Exposure (mg/kg/day)

and: 

Chronic Water Exposure = Chronic Water EEC (mg/L) x Drinking Water Consumption (L/day) 

(mg/kg/d) Body Weight (kg)

Table 18. Chronic Aggregate Risk

Population Subgroup Chronic 

Dietary 

NOAEL 

(mg/kg/day)

Chronic 

Dietary 

Exposure

(mg/kg/day)

Chronic 

Water

EEC

(mg/L)

DW 

Consumption 

(L/day)

Body

Weight

(kg)

Annual Avg 

Water 

Exposure

(mg/kg/day)

Chronic 

Aggregate 

MOE

US Population (total) 0.5 0.0019 0.02 2 70 0.00057 202

All Infants (<1 year old) 0.5 0.0017 0.02 1 10 0.002 135

Children 1-6 years old 0.5 0.0031 0.02 1 10 0.002 98

Children 7-12 years old 0.5 0.0021 0.02 1 10 0.002 122

Females 13-50 years old 0.5 0.0017 0.02 2 60 0.00067 211

Males 13-19 years old 0.5 0.0018 0.02 2 70 0.00057 211

Males 20+ years old 0.5 0.0019 0.02 2 70 0.00057 202

Seniors 55+ years old 0.5 0.0015 0.02 2 70 0.00057 241

6.0 CUMULATIVE RISK

The Food Quality Protection Act (1996) stipulates that when determining the safety of a 

pesticide chemical, EPA shall base its assessment of the risk posed by the chemical on, among 

other things, available information concerning the cumulative effects to human health that may
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result from dietary, residential, or other non-occupational exposure to other substances that have a 

common mechanism of toxicity. The reason for consideration of other substances is due to the 

possibility that low-level exposures to multiple chemical substances that cause a common toxic 

effect by a common mechanism could lead to the same adverse health effect as would a higher 

level of exposure to any of the other substances individually. A person exposed to a pesticide at a 

level that is considered safe may in fact experience harm if that person is also exposed to other 

substances that cause a common toxic effect by a mechanism common with that of the subject 

pesticide, even if the individual exposure levels to the other substances are also considered safe.

HED did not perform a cumulative risk assessment as part of this TRED for diquat 

dibromide because HED has not yet initiated a review to determine if there are any other chemical 

substances that have a mechanism of toxicity common with that of diquat dibromide. For 

purposes of this TRED, EPA has assumed that diquat dibromide does not have a common 

mechanism of toxicity with other substances.

On this basis, the registrant must submit, upon EPA’s request and according to a schedule 

determined by the Agency, such information as the Agency directs to be submitted in order to 

evaluate issues related to whether diquat dibromide shares a common mechanism of toxicity with 

any other substance and, if so, whether any tolerances for diquat dibromide need to be modified or 

revoked. If HED identifies other substances that share a common mechanism of toxicity with 

diquat dibromide, HED will perform aggregate exposure assessments on each chemical, and will 

begin to conduct a cumulative risk assessment once the final guidance HED will use for 

conducting cumulative risk assessments is available. 

HED has recently developed a framework that it proposes to use for conducting cumulative 

risk assessments on substances that have a common mechanism of toxicity. This guidance was 

issued for public comment on June 30, 2000 (65 FR 40644-40650) and is available from the OPP 

Website at: http://www.epa.gov/fedrgstr/EPA-PEST/2000/June/Day-30/6049.pdf In the draft 

guidance, it is stated that a cumulative risk assessment of substances that cause a common toxic 

effect by a common mechanism will not be conducted until an aggregate exposure assessment of 

each substance has been completed. The proposed guidance on cumulative risk assessment of 

pesticide chemicals that have a common mechanism of toxicity is expected to be finalized by

December 2001.

Before undertaking a cumulative risk assessment, HED will follow procedures for 

identifying chemicals that have a common mechanism of toxicity as set forth in the “Guidance for 

Identifying Pesticide Chemicals and Other Substances that Have a Common Mechanism of 

Toxicity” (64 FR 5795-5796, February 5, 1999).

7.0 DATA NEEDS/LABEL REQUIREMENTS
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All product chemistry data are required for the Syngenta 41.1% and 37.3% Formulation 

Intermediates (EPA Reg. Nos. 10-1062 and 100-1063). Magnitude of the residue in plants studies 

are required for sorghum aspirated grain fractions and soybean aspirated grain fractions.