UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON, D.C.  20460
                                                                      OFFICE OF
                                                            CHEMICAL SAFETY AND
\* MERGEFORMAT
                                                           POLLUTION PREVENTION

MEMORANDUM

Date:	 Aug 29, 2016

Subject:	Diquat Dibromide.  Revised Occupational and Residential Exposure Assessment for Registration Review.

PC Code:  032201
DP Barcode:  D434562
Decision Nos.: 512662
Registration No.: Multiple Registrations
Petition Nos.:  NA
Regulatory Action:  Registration Review Risk Assessment
Risk Assessment Type:  Single Chemical
Case No.:  0288
TXR No.:  N/A
CAS No.: 85-00-7, 2764-72-9 (cation)
MRID No.: N/A
40 CFR:  §180.226

FROM:	James Miller, Environmental Scientist
		Health Effects Division/Risk Assessment Branch 1 (HED; 7509P)

THRU:           Kelly Lowe, Acting Branch Chief
	Risk Assessment Branch I
	HED (7509P)

	Joshua Godshall, Biologist
	Exposure Science Advisory Committee (ExpoSAC) / HED

TO:		Bonnie Adler
		Pesticide Re-evaluation Division (PRD; 7508P)

Introduction
As part of Registration Review, the Pesticide Re-evaluation Division (PRD) of OPP has requested that HED evaluate the hazard and exposure data and conduct occupational and residential exposure assessments, as needed, to estimate the risk to human health that will result from the currently registered uses of pesticides.  This memorandum serves as HED's Registration Review risk assessment of the occupational and residential handler and post-application exposure and risk from the currently registered uses of diquat dibromide.

It is HED policy to use the best available data to assess exposure. Several sources of generic data were used in this assessment as surrogate data in the absence of chemical-specific data, including:  Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Outdoor Residential Exposure Task Force (ORETF) database, the Agricultural Handler Exposure Task Force (AHETF) database, the November 2015 Aquatic Use Standard Operating Procedure (SOP), and the Agricultural Reentry Task Force (ARTF) database. Some of these data are proprietary, and subject to the data protection provisions of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

This revised document supersedes previous versions and includes (1) updates to the assumptions for aquatic uses to reflect information received from the Army Corps of Engineers.

Note:  This revised memorandum was reviewed on 8/4/2016.

                               Table of Contents

1.0	Executive Summary	4
2.0	Risk Assessment Conclusions and Recommendations	7
  2.1	Summary of Risk Estimates	7
  2.2	Label Recommendations from Occupational Assessment	7
  2.3	Label Recommendations from Residential Assessment	8
  2.4	Data Deficiencies and Requirements	8
3.0	Hazard Characterization	9
4.0	Use Profile	13
5.0	Residential Exposure and Risk Estimates	15
  5.1	Residential Handler Exposure/Risk Estimates	16
  5.2	Residential Post-application Exposure/Risk Estimates	18
  5.3 	Residential Risk Estimates for Use in Aggregate Assessment	19
  5.4	Spray Drift	20
  5.5	Residential Bystander Post-Application Inhalation Exposure	21
6.0	Occupational Exposure and Risk Estimates	21
  6.1	Occupational Handler Exposure/Risk Estimates	21
  6.2	Occupational Post-application Exposure/Risk Estimates	30
    6.2.1	Occupational Post-application Inhalation Exposure/Risk Estimates	30
    6.2.2	Occupational Post-application Dermal Exposure/Risk Estimates.....................31
Appendix A. Summary of Occupational and Residential Non-cancer Algorithms..................33
Appendix B. Summary of Label Directions concerning Aquatic Uses...............................59
References.....................................................................................................60

1.0	Executive Summary

The active ingredient of diquat dibromide, 6, 7-dihydropyrido(1,2-a:2',1,-c) pyrazinediium dibromide, is a non-selective contact herbicide, desiccant and plant growth regulator. The oxidative activity, which occurs subsequent to formation of the oxygen radicals, rapidly destroys plant cell membranes.

Use Profile
Diquat dibromide is used as an herbicide/algaecide, and is formulated as a soluble concentrate (SC) and a ready to use liquid (RTU) intended for use on aquatic, terrestrial, and non-terrestrial weeds, and as a pre-harvest desiccant, post-harvest defoliant on various crops and on resistant dormant turf (Bermuda and Zoysia grass).  Diquat dibromide is applied by direct pouring, handheld or mechanical sprayer, injection below the water surface and directly into sewer pipes, aircraft, and ground equipment. Maximum application rates vary according to use description.  Maximum application rates for occupational use sites range from 0.25 lb ai/acre to 0.5 lb ai/acre for terrestrial, non-crop terrestrial, and farmland uses. For aquatic uses, the maximum rate for aerial application is 4 lb ai/acre-ft, while an application rate of 0.04 lb ai/gal was used for handheld equipment to lakes and ponds.  Maximum application rates for residential use sites range from 0.5 lb ai/acre to 0.01 lb ai/gal for gardens, trees, and turf (resistant dormant Bermuda and Zoysia) and up to 0.000092 lb ai/ft [2] for aquatic uses such as backyard ponds.

Exposure Profile
Occupational:  There is a potential for occupational exposure associated with handler (i.e., mixing, loading and applying) activities for the registered uses.  Based on application rates and label information, occupational exposure to diquat dibromide is expected to occur for short-(1 to 30 days) and intermediate-term (1 to 6 months) durations.  Chronic exposures are not expected and were not assessed.  Occupational post-application exposure is anticipated for the registered golf course use.  For the other registered uses (e.g., ground directed desiccant and the post-harvest defoliant), HED does not believes significant exposure will occur, and the handler exposures being assessed within this document for those uses will be protective of any post-application exposure.  Based on the Agency's current practices, a quantitative non-cancer occupational post-application inhalation exposure assessment was not performed for diquat dibromide at this time.  If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post-application inhalation exposure assessment for diquat dibromide. Furthermore, a spray drift assessment was conducted but not included in this assessment, whereas residential turf application exposure scenarios are protective. See section 5.4 for details.

The diquat dibromide product labels direct mixers, loaders, applicators and other handlers to wear long-sleeved shirt and long pants, coveralls, shoes plus socks, chemical-resistant gloves and protective eyewear such as goggles or face shield, chemical-resistant headgear for overhead exposure, chemical resistant apron when cleaning equipment and no respirator. However, for sewer treatments, product labels include a respirator for the exposure scenarios listed above. The restricted-entry interval (REI) is 24 hours for all registered products.

Residential:  There is a potential for residential exposure associated with handler (i.e., mixing, loading and applying and ready to use products) activities for the registered uses.  Based on application rates and label information, residential exposure to diquat dibromide is expected to occur for a short-term (1 to 30 days) duration.  Chronic exposures are not expected and were not assessed.  Short-term dermal post-application exposure is anticipated for adults and children performing activities on treated turf, in treated gardens, and in aquatic areas.  Inhalation and incidental ingestion exposure is anticipated for adults and children swimming in aquatic areas.  For children (1 to <2 years old), incidental oral [Hand to Mount (HTM), Object to Mouth (OTM), and Soil Ingestion (SI)] exposure is also anticipated based on the turf use.

Hazard Profile
Diquat dibromide is classified as Acute Toxicity Categories II or III via the oral, dermal, and inhalation routes.  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).

The following points of departure (PODs) have been chosen for diquat dibromide: 1) a no observed adverse effect level (NOAEL) of 3 mg/kg/day from a developmental toxicity study in rabbits for short-or intermediate-term dermal and incidental oral exposures; 2) a NOAEL of 0.1 ug/L from a subchronic inhalation toxicity study in rats; corresponding to human equivalent concentrations (HECs) of 4.4x10[-5] mg/L for occupational worker exposure and 5.9x10[-5] mg/L for residential handler and post-application exposure.  Subsequent human equivalent dose values of 0.0042 mg/kg/day and 0.0014 mg/kg/day were calculated for these occupational and residential exposure assessments, respectively.

The body weight appropriate for adult dermal and inhalation assessments is 80 kg, since the PODs and effects are not developmental/fetal effects and are not specific to females. Body weights of 57, 32, and 11 kilograms were used for the different child life-stages associated with residential post-application, incidental oral, and spray drift exposure scenarios.  A 0.3% dermal absorption factor was applied.  Diquat dibromide is classified as not likely to be carcinogenic to humans;" therefore, a cancer assessment was not conducted.

HED's level of concern (LOC) for non-cancer risks (i.e., level of concern for MOEs or Margins of Exposure) is defined by the uncertainty factors. Both residential and occupational dermal and incidental oral exposure scenarios utilized a 10x uncertainty factor for human to human extrapolation (UFH) and a 10x for animal to human extrapolation (UFA), for a total LOC of 100. Both residential and occupational inhalation exposure scenarios utilized a 10x uncertainty factor for human to human extrapolation (UFH) and a 3x for animal to human extrapolation (UFA), for a total LOC of 30.

Residential Exposure/Risk:
For most short-term residential handler and post-application exposure scenarios, there are no risk estimates of concern associated with the use of diquat dibromide (i.e., MOEs >= 100 for dermal or incidental oral, and MOEs >= 30 for inhalation).  However, the following inhalation exposure scenario presented risks of concern:

Inhalation
 Backpack sprayer applications to gardens, trees and turf (lawns) and aquatic uses for recreational/backyard ponds

Spray drift:
The existing turf post-application assessment is considered protective of spray drift exposure based on the maximum application rate on crops and the existing turf application rates; therefore, a separate quantitative spray drift assessment was not conducted.  Dermal and incidental oral post-application MOEs for turf were not of concern (MOEs >= 100). See section 5.4 for details.

Occupational Handler Exposure/Risk:
There are no dermal short- or intermediate-term occupational risk estimates of concern at baseline (i.e., no gloves) associated with the existing uses of diquat dibromide (i.e., MOEs >= 100).  Some occupational scenarios reached acceptable inhalation MOEs at baseline (i.e., no respirator); however, several exposure scenarios presented risk estimates of concern (MOE < 30) at baseline.

The following scenarios reached acceptable MOEs with the addition of a PF5 respirator:
 Mixing/Loading for aerial applications to typical field crops,
 Mixing/Loading for boom sprayer applications to aquatic areas (surface weeds),
 Mixing/Loading for groundboom applications to high acreage crops,
 Applying with groundboom to typical and high acreage field crops.
 Mixing/Loading/Applying for a backpack sprayer to rights of way and landscaping, turf/athletic fields, structural and industrial/commercial areas,
 Mixing/Loading/Applying for a mechanically-pressurized hand-wand application for the use on greenhouse ornamentals, roses, cut flowers landscaping turf, industrial and commercial areas including foundations, structural and aquatic areas.

The following scenarios reached acceptable MOEs with the addition of a PF10 respirator:
 Applying boom sprayer to aquatic areas (surface weeds),
  Applying mechanically pressurized handgun to rights of way, utilities, railroad and roadways,
 Flagger for typical and high acreage field crops, and
 Mixing/Loading/Applying for a mechanically-pressurized hand-gun application for use in orchards (in and around trees), industrial/commercial areas, and typical field crops.

The following scenarios do not reach acceptable MOEs even with maximum PPE and EC:
 Mixing/Loading for aerial applications to high acreage crops and aquatic areas,
 Mixer/Loader for boom sprayer applications to aquatic areas (submersed weeds) and
 Mixing/Loading/Applying for a mechanically-pressurized hand-gun application in greenhouses.

Occupational Post-application Exposure/Risk:
An occupational post-application assessment was conducted for exposure due to golf course maintenance activities; there were no risk estimates of concern (i.e., MOEs >= 100).  An assessment was not conducted for pre-, and post-harvest desiccant/defoliant burn down uses, turf applications to industrial areas nor for aquatic uses, whereas commercial workers associated with these activities are not expected to be in these areas post treatment.

Human Studies Review
This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical.  These data, which include studies from PHED 1.1, the AHETF, the ARTF, the draft aquatic SOP and the Residential SOPs ( Lawns and Turf, Gardens and Trees) are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements.  For certain studies, the ethics review may have included review by the Human Studies Review Board.  Descriptions of data sources, as well as guidance on their use, can be found at the Agency website.

 2.0	Risk Assessment Conclusions and Recommendations

There are no short- or intermediate-term occupational dermal risk estimates of concern associated with the registered uses of diquat dibromide.  However, risk estimates of concern exist for multiple inhalation occupational exposure scenarios. Furthermore, there are no short-term residential post-application swimmer or incidental oral risk estimates of concern, however multiple residential handler dermal and inhalation residential risk estimates of concern exist. There are no data gaps in the exposure database.

2.1	Summary of Risk Estimates

 The occupational handler exposure and risk estimates indicate that the dermal MOEs are not of concern to HED; however, there are inhalation MOEs that are of concern for several scenarios with the use of label-recommended PPE (i.e., no respirator) and with the highest level of PPE and/or mitigation (i.e., PF10 respirator) available.
 Occupational post-application dermal exposure and risk estimates were assessed for the golf course use and based on the current exposure assessment, an REI of 12 hours is necessary to reach acceptable MOEs (i.e., MOEs >= 100).  Current product label REIs are 24 hours; based on the acute toxicity of diquat dibromide, a REI of 24 hours would be sufficient under the current worker protection standard (WPS).
 The residential handler exposure and risk estimates indicate that the dermal MOEs are not of concern to HED; however there are inhalation MOEs that are of concern.
 The residential post-application exposure and risk estimates indicate that there are no risk estimates of concern.

2.2	Label Recommendations Residential

A summary of the risk estimates has been provided, and shows that there are residential risk estimates of concern for registered uses of diquat dibromide.

2.3 	Label Recommendations Occupational

A summary of the risk estimates has been provided, and shows that there are occupational risk estimates of concern for registered uses of diquat dibromide based on the use pattern and label-required personal protective equipment.

2.4	Data Deficiencies and Requirements

Dislodgeable Foliar Residue (DFR):  In accordance with 40CFR158, DFR data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post-application exposure to foliage. In the case of diquat dibromide, due to the nature of the application (ground-directed, pre-, post-harvest defoliant/desiccant), post-application exposure is not expected; therefore, DFR data are not required at this time.

Turf Transferable Residue (TTR):  In accordance with 40CFR158, TTR data are required for all occupational (e.g., sod farms, golf courses, parks, and recreational areas) or residential turf uses that could result in post-application exposure to turf.  In the absence of chemical-specific TTR data, EPA uses default values.  The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of all TTR data, available at the time, which resulted in the selection of revised liquid and granular default values for the fraction of the application rate available for transfer after a turf application (FAR).  These values are based on an analysis of 59 TTR studies performed with the Modified California Roller Method (36 studies using liquids, 11 studies using wettable powders/water dispersible granules, and 12 studies using granules).  The liquid results (N=131) indicate a range of FAR values from 0.0005% to 6.1 % and the granular results (N=37) indicate a range of 0.00064% to 0.69%.  In both the liquid and granular data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity); or many other difficult to quantify factors.  Although witnessed across multiple chemicals, this range in FAR values is not expected when considering TTR data for a single chemical.

HED selected 1% and 0.2% as high-end default values for liquid and granular products, respectively.  Because TTR data are not available for [diquat dibromide], EPA is using the default value of [1%].  Although there may be a small degree of uncertainty in the use of the default TTR value for [diquat dibromide] (i.e., there is a small chance that the  FAR value may exceed the applicable default value), it is likely that the health-protective aspects of EPA's [residential and/or occupational] post-application turf assessment methodology will more than compensate for this potential uncertainty (i.e., the methodology is likely to overestimate exposure by a factor greater than the factor than the highest measured FAR values exceed the defaults ).  For example,  when assessing residential post-application turf exposure, EPA assumes the following:  exposures occur to  zero-day (i.e., day of application ) residues every day of the assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs, it doesn't rain, the grass is not mowed, etc); individuals perform the same post-application activities performed in the turf transfer coefficient study day after day (e.g., tumbling, playing on turf with toys, etc.); and individuals engage in these post-application activities for  a high-end amount of time every day that is represented by data reflecting time children spend outdoors and not specifically engaged in activities on turf, when in actuality children do not spend all of their outdoor time on turf and high-end levels of activity will not occur every day.  Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that exposure is not being underestimated.

In the case of diquat dibromide; default assumptions were used in all calculations. However, a DFR "turf" study (MRID: 40917402) was submitted. In that study, turf clippings were gathered and DFR residues were measured. HED believes that although these DFR values are not based on the Modified California Roller Method, sampling methodology was verified and therefore satisfies the study data requirements.

Since the estimated residential turf post-application exposure for residential turf/mower/golf course using default TTR values for diquat dibromide is not minimal in comparison to the level of concern (i.e., the calculated MOE is not greater than 10 times higher than the level of concern, MOE = 150 compared to the LOC of 100), future refinements of this post-application exposure for diquat dibromide may be necessary due to increased use of diquat dibromide or advances in EPA risk assessments.

3.0	Hazard Characterization

The eye was a target organ following subchronic and chronic oral exposures in rats, mice, and dogs causing opacity, lesions, discharge, and cataracts at doses greater than those eliciting clinical signs.  The physical properties of diquat indicate it is highly hydrophilic and such chemicals will often cause ocular effects due to the high water content of the eye.  Clinical signs and body weight decrements were noted throughout the database following acute, subchronic, and chronic exposures to diquat.  The majority of the clinical signs were associated with ocular toxicity (e.g., eye discharge, opaque eyes) or general systemic toxicity (e.g., diarrhea, urinary incontinence, lack of grooming).  In several studies, including the acute neurotoxicity study, there was evidence of potential neurotoxicity based on increased incidence of piloerection, abnormal posture and gait, and subdued behavior; however, these signs are most likely indicative of overt toxicity rather than direct neurotoxicity since they were only seen at the highest dose tested and are consistent with those observed at overtly toxic doses in other studies following diquat exposure.

There was no evidence of increased pre- or post-natal susceptibility.  The maternal/parental effects were consistent with those seen in the toxicological database, and observed at doses at or below those producing developmental (decreased fetal body weights and skeletal variations) or offspring (reduced number of live pups, kidney lesions, and body weight decrements) effects.
An acceptable route-specific inhalation subchronic toxicity study in rats is available for diquat.  Portal of entry effects occurred at doses much lower than those eliciting oral toxicity and consisted of microscopic lung lesions and increased lung weights in both sexes.

Acute Toxicity
Diquat dibromide is classified as Acute Toxicity Categories II or III via the oral, dermal, and inhalation routes. 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 dibromide are shown in Table 3.1.

Table 3.1. Acute Toxicity of Diquat Dibromide.
                                 Guideline No.
                                  Study Type
                                   MRID No.
                                    Results
                               Toxicity Category
                                   870.1100
                                  Acute Oral
                                   00081506
                             rat LD50 = 810 mg/kg
                             rat LD50 = 600 mg/kg
                                      III
                                   870.1200
                                 Acute Dermal
                                   00010014
                           rabbits LD50 = 262 mg/kg
                           rabbits LD50 = 315 mg/kg
                          rabbits LD50 = 288.5 mg/kg
                                      II
                                   870.1200
                                 Acute Dermal
                                   49797702
                           Rat LD50 > 2000 mg/kg
                       (diquat ion LD50 > 424 mg/kg)
                                   II or III
                                   870.1200
                                 Acute Dermal
                                (non-guideline)
                                   00061634
                                 LD50 between
                         200 and 400 mg diquat ion/kg
                                      II
                                   870.1300
                               Acute Inhalation
                                   00026385
                             rat LC50 = 0.80 mg/L
                             rat LC50 = 1.09 mg/L
                             rat LC50 = 0.97 mg/L
                                      III
                                   870.2400
                           Primary Eye  Irritation
                                   00081507
                       Rabbit slight to severe irritant
                                      II
                                   870.2500
                            Primary Skin Irritation
                                   00107903
                               slight-irritating
                                      IV
                                   870.2600
                             Dermal Sensitization
                                   00107903
                               not a sensitizer
                                      N/A
With the exception of the dermal sensitization study, which was conducted with the technical diquat (Diquat Herbicide Concentrate), the above studies were conducted with the end-use products [Diquat Water Weed Killer and Diquat 2 Spray (eye irritation study only)] and not in terms of the diquat ion.  Because the only difference between the technical diquat and the end-use products is 2.15% water, studies with the end-use products have been accepted to satisfy the generic data requirements for acute studies.  The above LD and LC values are mostly expressed in terms of the test material and not, as is commonly done with diquat, in terms of the diquat cation.

Toxicological PODs Used for Risk Assessment
The following points of departure (PODs) have been chosen for diquat dibromide: 1) a no observed adverse effect level (NOAEL) of 3 mg/kg/day from a developmental toxicity study in rabbits for short-or intermediate-term dermal and incidental oral exposures; 2) a NOAEL of 0.01 ug/L from a subchronic inhalation toxicity study in rats.  See Tables 3.2 and 3.3 for details regarding selected residential and occupational PODs, respectively.

HECs for residential and occupational inhalation scenarios were derived using the NOAEL and the regional deposited dose ratio (RDDR).  The RDDR accounts for the particulate diameter [mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD)] and estimates the different dose fractions deposited along the respiratory tract.  The RDDR also accounts for interspecies differences in ventilation and respiratory tract surface areas.  For the subchronic inhalation toxicity study with diquat, a RDDR was estimated at 0.591 based the pulmonary effects seen at the LOAEL of 0.49 ug/L, with a MMAD of 1.9 um and GSD of 1.9.

HECs of 4.4x10[-5] mg/L for occupational worker exposure and 5.9x10[-5] mg/L for residential handler and outdoor post-application exposures were obtained.  Subsequent human equivalent dose values of 0.0042 mg/kg/day and 0.0014 mg/kg/day were calculated for these occupational and residential exposure assessments, respectively.  HEC and human equivalent dose calculations are summarized in Table 3.4.  The standard interspecies extrapolation uncertainty factor can be reduced from 10X to 3X due to the calculation of HECs accounting for pharmacokinetic (not pharmacodynamic) interspecies differences.  Therefore, the LOC for inhalation exposures is 30 (3X for interspecies extrapolation, 10X for intra-species variation, and 1X for FQPA SF when applicable).

Table 3.2 Summary of Toxicological Doses and Endpoints for Diquat Dibromide for Use in Dietary and Non-Occupational Human Health Risk Assessments
                              Exposure/ Scenario
                           Point of Departure (POD)
                        Uncertainty/FQPA Safety Factors
                RfD, PAD, Level of Concern for Risk Assessment
                        Study and Toxicological Effects
Incidental Oral
Short-Term
(1-30 days) and Intermediate-Term (1-6 months)
                              NOAEL = 3 mg/kg/day
                                   UFA = 10X
                                   UFH = 10X
                                   FQPA = 1X
Residential LOC = 100
Developmental Toxicity Study in Rabbits
LOAEL = 10 mg /kg/day based on clinical signs
Dermal
Short-Term
(1-30 days) and Intermediate-Term (1-6 months)
                              NOAEL = 3 mg/kg/day

                           Dermal absorption factor
                                 (DAF) = 0.3%
                                   UFA = 10X
                                   UFH = 10X
                                   FQPA = 1X
Residential LOC = 100
Developmental Toxicity Study in Rabbits
LOAEL = 10 mg /kg/day based on  clinical signs
Inhalation
Short-Term
(1-30 days) and Intermediate-Term (1-6 months)
                               NOAEL = 0.1 ug/L
                                 (0.0001 mg/L)
                                   UFA = 3X
                                   UFH = 10X
                                   FQPA = 1X
Residential LOC = 30
Subchronic Inhalation Toxicity Study in Rats
LOAEL = 0.49 ug/L (0.00049 mg/L) based on increased mean lung weights and microscopic lesions in the lung
Cancer (oral, dermal, inhalation)
Classified as "Category E - evidence of non-carcinogenicity for humans"
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intra-species).  FQPA SF = FQPA Safety Factor.  PAD = population adjusted dose (a = acute, c = chronic).  RfD = reference dose (a= acute, c = chronic).  MOE = margin of exposure.  LOC = level of concern.

Table 3.3 Summary of Toxicological Doses and Endpoints for Diquat Dibromide for Use Occupational Human Health Risk Assessments
                              Exposure/ Scenario
                              Point of Departure
                          Uncertainty Safety Factors
                RfD, PAD, Level of Concern for Risk Assessment
                        Study and Toxicological Effects
Dermal
Short-Term
(1-30 days) and Intermediate-Term (1-6 months)
                              NOAEL = 3 mg/kg/day

                           Dermal absorption factor
                                 (DAF) = 0.3%
                                   UFA = 10X
                                   UFH = 10X
Occupational LOC = 100
Developmental Toxicity Study in Rabbits
LOAEL = 10 mg /kg/day based on clinical signs.
Inhalation
Short-Term
(1-30 days) and Intermediate-Term (1-6 months)

                        NOAEL = 0.1 ug/L (0.0001 mg/L)

                                   UFA = 3X
                                   UFH = 10X
Occupational LOC = 30
Subchronic Inhalation Toxicity Study in Rats
LOAEL = 0.49 ug/L (0.00049 mg/L) based on increased mean lung weights and microscopic lesions in the lung
Cancer (oral, dermal, inhalation)
Classified as "Category E - evidence of non-carcinogenicity for humans"
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no observed adverse effect level.  LOAEL = lowest observed adverse effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intra-species).  FQPA SF = FQPA Safety Factor.  PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose (a = acute, c = chronic).  MOE = margin of exposure.  LOC = level of concern.

Table 3.4 Summary of Inhalation Calculations for Human Equivalent Concentrations and Doses for Diquat Dibromide.
                                  Population
                                   Scenario
                        Toxicity Duration Adjustment[a]
                       Human Equivalent Concentration[b]
                             Human Equivalent Dose

                                   hours/day
                                   days/week
                                     mg/L
                                    mg/m[3]
                                   mg/kg/day
                                 Occupational
                                    Handler
                                       8
                                       5
                                  4.43x10[-5]
                                     0.044
                                    0.0042
                                  Residential
                                    Handler
                                      NA
                                      NA
                                  5.91x10[-5]
                                     0.059
                                    0.0014

                           Outdoor post-application
                                      NA
                                      NA
                                  5.91x10[-5]
                                     0.059
                                      NA

                            Indoor post-application
                                      NA
                                       7
                                  4.22x10[-5]
                                     0.042
                                      NA

                                   Bystander
                                      24
                                       7
                                  1.06x10[-5]
                                     0.011
                                      NA
a. Toxicity duration adjustment from 6 hours/day, 5 days/week exposure in rat study.
b. Human equivalent concentrations calculated using duration adjustments, when applicable, and a pulmonary regional deposited dose ratio (RDDR) of 0.591, which was obtained with a mass median aerodynamic diameter (MMAD) of 1.9, a geometric standard deviation (GSD) of 1.9, and the default combined sex body weight for Fischer 344 rats of 152 g.
NA = not applicable (the expected duration of the exposure scenario is less than the duration of available inhalation toxicity studies; downward adjustments are not permitted).

Absorption:
A dermal absorption factor of 0.3% was estimated from a human dermal absorption study (MRID 43736616).

Body Weight:
The standard body weight for the general population (80 kg) was used for all exposure scenarios covered in this risk assessment since the endpoints selected were not developmental and/or fetal effects. Body weights of 57, 32, and 11 kilograms were used for the different child life-stages associated with residential post-application, incidental oral, and spray drift exposure scenarios.

4.0	Use Profile

Table 4.1 provides a summary of the registered uses of diquat dibromide.

Table 4.1.  Summary of Directions for Use of Diquat Dibromide.
                       Applic. Timing, Type, and Equip.
                                     Crop
                            Formln. [EPA Reg. No.]
                                Applic. Rate[1]

                           Max. No. Appl. Per Season
                          Max. Seasonal Appl. Rate[2]

                             Pre-harvest Interval
                                     (PHI)
                                    (Days)
                        Use Directions and Limitations
                  Use Site 1 (Terrestrial Crop and Farmland)

                                 Pre-harvest/
                                 desiccation
                                  Ground and
                                    Aerial
                               Alfalfa, Clover,
                                  (Seed crop)
                                      SC
                             (EPA Reg.# 100-1061)

                                     0.5
                                  lb ai/Acre

                                       2
                                1.0  lb ai/Acre
                                       3
                   Do not apply through irrigation systems.
               Do not graze or feed treated forage to livestock
      Do not use seed from treated plants for food, feed or oil purposes

                                     24C:
                                  FL- 000009
                                   SC-000005

                                Potato, Canola

                                       7

                              Non-bearing crops:
                             Ground Directed Spray
                                Crop Groups [3]
                   4, 13-07, 14-12, 10-10, 99, 12-12, 11-10
                                      SC
                             (EPA Reg.# 100-1061)

                                       5
                                2.5 lb ai/Acre
                                      365

                            Post-Harvest burn down:

                                  Groundboom.
                                 Tomato Vines

                                0.38 lb ai/Acre
                                       2
                                0.75 lb ai/Acre
                                      N/A

                               Cantaloupe Vines
                                      SC
                             (EPA Reg.# 100-1061)

                                0.25 lb ai/Acre

                                0.5 lb ai/Acre

                         Cucumber, Squash, Watermelon

                                0.38 lb ai/Acre

                                0.75 lb ai/Acre

                             Acorn squash, Peppers

                                0.5 lb ai/Acre

                                 1 lb ai/Acre

                                 Weed control:
                                  Middle Rows
                             Ground Directed Spray
                        Eggplant, Green Pepper, Tomato
                                      SC
                             (EPA Reg.# 100-1061)

                                  0.5 lb ai/A

                                       2
                                 1 lb ai/Acre
                                      30
                     Do not apply when wind speed exceeds
                                     5 mph

                                     24C:
                                   FL-000010
                                   PR-030001
                            Pre-Harvest desiccation

                               Ground and Aerial
Carrots, Coriander, Radishes, Spinach, Sugar Beets, Table Beet, Turnips, Calendulas
                                      SC
                             (EPA Reg.# 100-1061)

                                  0.5 lb ai/A

                                       1
                                0.5 lb ai/Acre
                                       3
Do not apply through irrigation systems. Use only on non-edible oilseed varieties of calendula.

                                     24C:
                                   WA-040011
                                   OR-080025
                                   ID-100006
                                   MN-090006
                    Non-Crop or Non-Planted Areas on Farms

                                Ground Directed
Fence Lines, Farmyards, Farm Buildings, Fuel Storage Areas, barrier Strips, and Equipment Areas around ponds, lakes and drainage ditches on farms.
                                      SC
                             (EPA Reg.# 100-1061)

                                0.5 lb ai/Acre
                                      10
                                 5 lb ai/Acre
                                      N/A
For spot treatments, apply 2 qt product/100 gallon water (or 22 ml product/1 gallon water)
                       Use Site 2 (Non-Crop Terrestrial)
                            Pre-harvest Desiccation
                                Ground directed
                             Ornamental seed crops
                                      SC
                                  (EPA Reg.#
                              100-1091, 100-1390)
                                0.5 lb ai/Acre
                                       3
                                1.5 lb ai/Acre
                                      N/A
Do not apply through any type of irrigation system. For seed crop only. Not for food or fiber crops. Not allowed in California.

Commercial Greenhouse (beneath benches), field grown and container stock and other similar areas

                 Landscape, Industrial, Commercial  areas [4]
                            including golf courses

                                Turf Renovation

                                       2
                                 1 lb ai/Acre

                        Dormant Established Turf Grass

           Pre-plant, Pre-emergence,   Post-Emergence Directed Spray
                          (Spot/Broadcast Treatments)
Commercial Greenhouse (beneath benches), field grown and container stock and other similar areas

                            0.01 to 0.04 lb ai/gal
                                       5
                                 2 lb ai/Acre

Not for food or fiber crops. Avoid spray contact with foliage of food crops or ornamental plants or other desirable vegetation

       Landscape, Industrial, Commercial, Residential and Public Areas

              Use Site 3 (Aquatic - Occupational and Residential)
Aquatic Broadcast  around lakes, ponds, drainage ditches, reservoirs, marshes, canals and rivers

                      Floating and Marginal Surface Weeds
                                      SC
                                  (EPA Reg.#
                              100-1091, 100-1390)
                              4 lb ai/ Acre/1ft
                                      10

       See table in Appendix B for extensive directions and limitations.
                                    24C [5]
                                   FL-030006
                                   FL-110009
                                   ID-070012
                                   AL-07001
                                   GA-080004
                                   NY-030001
                                   NY-120007

                                Submersed Weeds

                             4 lb ai/ Acre/4 feet

                 Standing and Flowing Water - Submerged Weeds

                         Still Water - Submerged Weeds

                         Still Water - Floating Weeds

                              1.5 lb ai/ Acre/3ft

                       Still Water - Duckweed, Cattails

                               2 lb ai/ Acre/3ft

                                   Injection
                or High Pressure Spray into Sewer Systems Pipes
                          Tree Root Mass in Pipelines
                                      SC
                                  (EPA Reg.#
                                    64898-8
                                0.01 lb ai/gal
                                      N/A
                                      N/A
                                      N/A
                                      N/A
                                 Aquatic [6]
                                Spot Treatment
                          Floating and Marginal Weeds
                                      SC
                                  (EPA Reg.#
                              100-1091, 100-1390)
                                0.04 lb ai/gal

                                40 lb/Sq. Acre
                                      N/A
                                See Appendix A
                                 Aquatic Uses

                             0.000092 lb ai ft[2]

                                      N/A

                          Use Site 3 (Residential)[7]
                         Manually Pressurized Handwand
                              Gardens/Trees/Turf
                                      SC
                                  (EPA Reg.#
                              100-1091, 100-1390)
                                0.01 lb ai/gal
                                      N/A
                                      N/A
                                      N/A
                                      N/A

                                0.5 lb ai/Acre

                               Backpack Sprayer

                                0.01 lb  ai/gal

                             Trigger-spray Bottle

                            0.0025 lb ai/bottle[8]

1, 2 Rate = Maximum application rates specified on labels (EPA Reg. # 100-1061 "Master Label", 1091, 1390, and "sewer uses" 64898-8); Use pattern matrix supplied by email:  PRD 9/5/2014, 7/30/2014, and SRRD use index 8/28/2014; TRED (D281890). For information concerning the 1,125 gallons used for sewer applications See Memorandum, DP # 357118 titled, Metam Sodium: Third Revision of the HED Human Risk Assessment, Dated April 30, 2009.
3. Crop groups (4, 13-07, 14-12, 10-10, 99, 12-12, 11-10): vegetable, leafy, except brassica; fruit, berry and small fruit; nut, tree; fruit, citrus; fruit, stone; fruit, pome.
4. Areas of use; around trees ornamental gardens, beneath commercial greenhouse Benches. Other Non-Crop Areas: buildings, parking lots, cart paths, patios, dividers, pipelines, driveways, public utility lines, electric utilities, pumping stations, fence lines, railroad beds/yards, golf courses, rights of way, highways, roads, landscape beds, roadsides, lawns, transformer stations and substations, medians, walkways, non-flooded portions of ponds, lakes and ditches.
5. Labels direct 24C registrations to not treat water where depth is 3 feet or less and to not apply by air.
6. Label rate: 4 lb ai/Acre x Acre/43,560 sq ft = 0.000092 lb ai/ft sq.
7. Residential use information: See TRED (D281890) for specifics
8. TRED - (D281890): Trigger Sprayer:  high end = 0.01 lb ai.gal, so: 0.01 lbs ai/gal x gal/128 fl. oz. x 32 fl. oz/bottle = 0.0025 lb ai/bottle (32 fl. oz).
9. REI = 24 hr. (for occupational uses)

5.0	Residential Exposure and Risk Estimates

Residential uses have been reassessed in this documents to reflect updates to HED's 2012 Residential SOPs and the November 2015 Aquatic use SOP along with policy changes for body weight assumptions. The revision of residential exposures will impact the human health aggregate risk assessment for diquat dibromide.

5.1	Residential Handler Exposure/Risk Estimates

HED uses the term "handlers" to describe those individuals who are involved in the pesticide application process.  HED believes that there are distinct tasks related to applications and that exposures can vary depending on the specifics of each task.  Residential handlers are addressed somewhat differently by HED as homeowners are assumed to complete all elements of an application without use of any protective equipment.

The quantitative exposure/risk assessment developed for residential handlers is based on the following scenarios:

Mixing/Loading/Applying:

 Manually Pressurized Handwand: Gardens/Trees/Turf (around the home and garden), residential lawns, ornamentals, and greenhouses. Aquatic herbicide/algaecide uses include Recreational/back yard ponds.
 Backpack Sprayer: Gardens/Trees/Turf (around the home and garden). Aquatic herbicide/algaecide uses include Recreational/back yard ponds.

Applying:

 Trigger-Spray Bottle: Ready-to-use (R-T-U); Gardens/Trees/Turf (around the home and garden).

Residential Handler Exposure Data and Assumptions
A series of assumptions and exposure factors served as the basis for completing the residential handler risk assessments.  Each assumption and factor is detailed below.

Application Rate:
See table 4.1 for specifics.

Unit Exposures and Area Treated or Amount Handled:
Unit exposure values and estimates for area treated or amount handled were taken from HED's 2012 Residential SOPsand the November 2015 Aquatic use SOP.

Exposure Duration:
Residential handler exposure is expected to be short-term in duration.  Intermediate-term exposures are not likely because of the intermittent nature of applications by homeowners.
Residential Handler Non-Cancer Exposure and Risk Estimate Equations
The algorithms used to estimate exposure and dose for residential handlers can be found in Appendix A and/or the 2012 Residential SOPs and the November 2015 Aquatic use SOP.

Summary of Residential Handler Non-Cancer Exposure and Risk Estimates
For most short-term residential handler and post-application exposure scenarios, there are no risk estimates of concern associated with the use of diquat dibromide (i.e., MOEs >= 100 for dermal or incidental oral, and MOEs >= 30 for inhalation). However, the following inhalation exposure scenarios presented risks of concern:
 Backpack sprayer applications to gardens, trees and turf (lawns)
 Backpack sprayer applications for aquatic uses for recreational/backyard ponds.

Table 5.1.1.  Residential Handler Non-cancer Exposure and Risk Estimates for diquat dibromide.
                               Exposure Scenario
                        Dermal Unit Exposure (mg/lb ai)
                      Inhalation Unit Exposure (mg/lb ai)
                                     Max.
                                     App.
                                    Rate[1]
                    Area Treated or Amount Handled Daily[2]
                                    Dermal
                                  Inhalation

                              Dose (mg/kg/day)[3]
                                    MOE[4]
                                  (LOC = 100)
                              Dose (mg/kg/day)[5]
                                    MOE[6]
                                   (LOC =30)
                 Mixer/Loader/Applicator (Soluble Concentrate)
                        Manually-pressurized Handwand/
                        Handgun  to Turf/Gardens /Trees
                                      63
                                     0.018
                                     0.01
                                   lb ai/gal
                                     5 gal

                                    0.00012
                                    25,000
                                    0.000011
                                      120
                           Backpack Sprayer to Turf

                                      130

                                     0.14
                                     0.01
                                   lb ai/gal

                                    0.00024
                                    12,000
                                   0.000088
                                      16
                     Backpack Sprayer to Gardens and Trees

                             Trigger-Spray bottle
                             to Gardens and Trees
                                     85.1
                                     0.061
                                    0.0025
                                    lb ai/
                                   bottle[7]
                                   2 bottles
                                   0.000016
                                    190,000
                                   0.0000038
                                      370
                             Trigger-Spray bottle
                                 to Lawns/Turf

                                   1 bottle
                                   0.000008
                                    380,000
                                   0.0000019
                                      730
                                 Aquatic Areas
                         Manually-pressurized Handwand
                                      63
                                     0.018
                             0.000092 lb ai/ft[2]
                                   500 ft[2]
                                    0.00011

                                    28,000

                                    0.00001

                                      140

                               Backpack Sprayer
                                      130
                                     0.14
                             0.000092 lb ai/ft[2]
                                   500 ft[2]
                                    0.00022
                                    13,000
                                   0.000081
                                      17
1. Application rates primarily based on use information provided by Registrant (supplied by email from PRD 9/5/2014, 7/30/2014).  The use information provided was noted to be based primarily on representative Section 3 and 24C labels from Syngenta Crop Protection.  In addition, information provided in the TRED (D281890) for diquat was used for the residential use information.
2.  Based on HED's Standard Operating Procedures for Residential Pesticide Exposure Assessment; Lawns/Turf (Feb. 2012) and   November 2015 Aquatic SOP.
3.  Dose (mg/kg/day) = daily unit exposure (mg/ - lb ai) x application rate (lb ai/area treated or amount handled) x Area treated or    amount handled * absorption factor (inhalation = 100 % and dermal = 0.3%) / -  body weight (80 kg).
4.  Dermal MOE = NOAEL (3 mg/kg/day) / daily dose (mg/ - kg/ - day).  Level of concern = 100.
5.  Inhalation Dose = daily unit exposure (mg/ - lb ai) x application rate (lb ai/area treated or amount handled) x Area treated or   amount handled / -  body weight (80 kg).
6.  Inhalation MOE = Human equivalent dose (0.0014 mg/kg/day) / daily dose (mg/ - kg/ - day).  Level of concern = 30.

5.2	Residential Post-application Exposure/Risk Estimates

There is the potential for post-application exposure for individuals exposed as a result of being in an environment that has been previously treated with diquat dibromide.  The quantitative exposure/risk assessment for residential post-application exposures is based on the following scenarios:

 Lawns and Turf:
 High contact activities, mowing and golfing (used on resistant dormant turf (Bermuda and Zoysia grass) for weed control.
 Incidental Oral: Hand to mouth (HtM), Object to Mouth (OtM), and Soil Ingestion (SI)

Gardens and Trees:
 Garden activities

Aquatic Activities:
 Swimming

The lifestages selected for each post-application scenario are based on an analysis provided as an Appendix in the 2012 Residential SOPs.

Application Rate:
See table 4.1 for details.

Exposure Duration:
Residential post-application exposure is expected to be short-term in duration.  Intermediate-term exposures are not likely because of the intermittent nature of applications by homeowners.

Residential Post-application Non-Cancer Exposure and Risk Equations
The algorithms used to estimate residential post-application exposure and dose can be found in Appendix A and/or the 2012 Residential SOPs.

Summary of Residential Post-application Non-Cancer Exposure and Risk Estimates
For calculation of residential post-application exposure, a developmental study was used for the dermal and incidental oral route based on clinical signs, while a route-specific inhalation study was used for the inhalation route based on lesions in the lung and lung weights. Therefore, dermal and incidental oral exposures are combined, whereas they are based on the same effects and have the same NOAEL of 3 mg/kg/day, however, inhalation exposure will not be combined. The incidental oral scenarios (i.e., hand-to-mouth and object-to-mouth) should be considered inter-related and it is likely that they occur interspersed amongst each other across time.  Combining these scenarios with the dermal exposure scenario would be overly-conservative because of the conservative nature of each individual assessment.  Therefore, the post-application exposure scenarios that were combined for children 1 < 2 years old are the dermal and hand-to-mouth scenarios.  The residential post-application exposures are summarized in tables 5.2.1 and 5.2.2.  All dermal and incidental oral MOEs are >= 100.

Table 5.2.1.  Residential Post-application Non-cancer Exposure and Risk Estimates for Diquat Dibromide.
                                   Lifestage
                      Post-application Exposure Scenario
                              Application Rate[1]
                              Dose (mg/kg/day)[2]
                                    MOEs[3]
                                Combined Routes
                         (X: included in Combined MOE)
                               Combined MOEs[4]

                                   Use Site
                          Route of Exposure/Activity

                                     Adult

                                  Lawns and
                                     Turf

                                  Lawns and
                                     Turf

                       Dermal / High Contact Activities

                                     0.5
                                  lb ai/Acre

                                     0.5
                                  lb ai/Acre
                                    0.00060
                                     5,300
                                      N/A
                                      N/A

                                Dermal / Mowing

                                   0.000012
                                    260,000
                                      N/A

                               Dermal / Golfing

                                   0.000044
                                    68,000
                                      N/A

                                     Child
                             1 to < 2 years old

                                     Child
                             1 to < 2 years old

                       Dermal / High Contact Activities

                                    0.0011
                                     2,700
                                       X
                                      350

                        Incidental oral / hand to mouth

                                    0.0076
                                      390
                                       X

                       Incidental oral / Object to mouth

                                    0.00023
                                    13,000
                                      N/A
                                      N/A

                       Incidental oral / soil ingestion

                                    1.7E-05
                                    180,000
                                      N/A

                                     Child
                            11 to < 16 years old
                                Lawns and Turf
                                Dermal / Mowing
                                      0.5
                                   lb ai/Acre
                                   0.000013
                                    230,000
                                      N/A
                                      N/A
                                     Child
                                 11 to < 16
                                   Years old

                               Dermal / Golfing

                                    0.00052
                                    58,000
                                      N/A

                                     Child
                                 6 to < 11
                                  Years old

                                   0.000060
                                    50,000
                                      N/A
                                      N/A
                                     Adult
                                    Gardens
                              General Activities

                                    0.00096
                                     3,100
                                      N/A

                                     Child
                                6 < 11 years
                                    Gardens
                              General Activities

                                    0.00070
                                     4,600

                                     Adult
                                    Aquatic
                                  (swimming)
                                  Inhalation
                                   0.000092
                                 lb ai/ft [2]
                                   7.75E-12
                                   1.80E+08
                                      N/A
                                   1.80E+08

                                    Dermal

                                   7.17E-09
                                   4.20E+08
                                       X
                                   4.20E+08

                                   Ingestion

                                   2.88E-06
                                   1.00E+06
                                       X

                                     Child
                             3 to < 6 years old

                                  Inhalation

                                   5.35E-11
                                   2.62E+07
                                      N/A
                                   2.62 E+07

                                    Dermal

                                   2.94E-08
                                   1.00E+08
                                       X
                                   1.02E+08

                                   Ingestion

                                   3.03E-05
                                   9.90E+04
                                       X

1	Application rates primarily based on use information provided by Registrant (supplied by email from PRD 9/5/2014, 7/30/2014).  The use information provided was noted to be based primarily on representative Section 3 and 24C labels from Syngenta Crop Protection.  In addition, information provided in the TRED (D281890) for diquat was used for the residential use information.
2	Dose (mg/kg/day) equations provided in Appendix [A]. Lawns/Turf, Gardens/Trees, Aquatic (swimming).
3	MOE = POD (mg/kg/day) / Dose (mg/kg/day).
4	Combined MOE = POD (3 mg/kg/day) / (dermal dose + incidental oral dose).

5.3 	Residential Risk Estimates for Use in Aggregate Assessment

There were certain scenarios that did not reach the LOC of 100 for dermal and 30 for inhalation, therefore only the residential exposure scenarios that were not of concern (MOE >= 100 for dermal and 30 for inhalation) have been recommended for the aggregate assessment.
Table 5.3.1 reflect the residential risk estimates that are recommended for use in the aggregate assessment for diquat dibromide.

 The recommended residential exposure for use in the adult aggregate assessment reflects dermal exposures from high contact activities on outdoor treated turf.

 The recommended residential exposure for use in the children 1 to 2 years old aggregate assessment reflects exposures from high contact activities on outdoor treated turf.

Table 5.3.1 Recommendations for the Residential Exposures for the Diquat Dibromide Aggregate Assessment.
                                   Lifestage
                               Exposure Scenario
                              Dose (mg/kg/day)[1]
                                    MOE [2]

                                    Dermal
                                  Inhalation
                                     Oral
                                     Total
                                    Dermal
                                  (LOC = 100)
                                 Inhalation[3]
                                  (LOC = 30)
                                     Oral
                                     Total
                                     Adult
              Postapp: High contact activities from treated turf
                                    0.0006
                                      N/A
                                      N/A
                                      N/A
                                     5,300
                                      N/A
                                      N/A
                                      N/A
                                    Child
                                   (1 to 2
                                  years old)
                   High contact activities from treated turf
                                    0.0011
                                      N/A
                                    0.0076
                                     0.0087
                                     2,700
                                      N/A
                                      390
                                      350
1.	Dose = the highest dose for each applicable life stage of all residential scenarios assessed.  Total = dermal + incidental oral (where applicable).
2. Total MOE = [3.0 mg/kg/day / (combined dermal) + (oral dose)], where applicable.
3. Inhalation endpoint is based on a different study with different effects thus not combined.

5.4	Spray Drift

Off-target movement of pesticides can occur via many types of pathways and it is governed by a variety of factors.  Sprays that are released and do not deposit in the application area end up off-target and can lead to exposures to those it may directly contact. They can also deposit on surfaces where contact with residues can eventually lead to indirect exposures (e.g., children playing on lawns where residues have deposited next to treated fields). The potential risk estimates from these residues can be calculated using drift modeling onto 50 feet wide lawns coupled with methods employed for residential risk assessments for turf products.

The approach to be used for quantitatively incorporating spray drift into risk assessment is based on a premise of compliant applications which, by definition, should not result in direct exposures to individuals because of existing label language and other regulatory requirements intended to prevent them.  Direct exposures would include inhalation of the spray plume or being sprayed directly.  Rather, the exposures addressed here are thought to occur indirectly through contact with impacted areas, such as residential lawns, when compliant applications are conducted.  Given this premise, exposures for children (1 to 2 years old) and adults who have contact with turf where residues are assumed to have deposited via spray drift thus resulting in an indirect exposure are the focus of this analysis analogous to how exposures to turf products are considered in risk assessment.

Several diquat dibromide products have existing labels for use on turf, thus it was considered whether the risk assessment for that use may be considered protective of any type of exposure that would be associated with spray drift.  It should be noted that the registered residential uses on turf result in exposure greater than potential exposure from spray drift; therefore, no new residential assessment needs to be completed.  If the maximum application rate on crops adjusted by the amount of drift expected is less than or equal to existing turf application rates, the existing turf assessment is considered protective of spray drift exposure.  The currently registered maximum single application rate of diquat dibromide for crops is 0.5 lb ai/A.  The highest degree of spray drift noted for any application method immediately adjacent to a treated field (Tier 1 output from the aerial application using fine to medium spray quality) results in an deposition fraction of 0.26 of the application rate.  A quantitative spray drift assessment for diquat dibromide is not required because the maximum application rate to a crop/target site multiplied by the adjustment factor for drift of 0.26 is less than the maximum direct spray residential turf application rate (0.5 lb ai/A) for any diquat dibromide products.  The turf post-application MOEs have been previously assessed and are based on the revised SOPs for Residential Exposure Assessment (i.e., see above in Section 5.2).

For aquatic uses, subsurface, bottom placement, and surface applications may be made.  The only application with the potential for spray drift is surface application as a spray. Although the label does not prohibit the use of aerial applications for aquatic areas, it is unlikely aerial applications would be made given the types of water bodies the product is being applied to and the alternative application options (handheld application equipment).

5.5	Residential Bystander Post-Application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to individuals nearby pesticide applications.  The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP's final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html).  The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is required for diquat dibromide.

6.0	Occupational Exposure and Risk Estimates
6.1	Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process.  HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each task.  Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the registered uses.  The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios:

 Mixing/Loading for aerial application on typical and high acreage crops and aquatic uses,
 Mixing/Loading for groundboom application on typical and high acreage crops, turf (golf courses), and orchard/vineyard,
 Mixing/Loading for boom sprayer applications for aquatic uses,
 Mixing/Loading for injection and spray applications for tree root control in sewer lines,
 Applying via aerial equipment on typical and high acreage crops, orchard/vineyard, and aquatic uses,
 Applying via groundboom on turf (golf course), field grown ornamentals, orchards, greenhouses, and typical and high acreage field crops,
 Applying via boom sprayer on aquatic uses,
 Applying via mechanically-pressurized handgun on rights of way/industrial areas,
 Applying via trigger-spray bottle on foundations/perimeters, landscaping, and turf (lawns, athletic fields, parks, etc.),
 Mixing/Loading/Applying via a backpack sprayer for orchard/vineyards, greenhouse use, rights-of ways, landscaping, turf, structural areas (bridges, shipyards), industrial/commercial areas, foundations/perimeter, and aquatic areas (lakes/ponds),
 Mixing/Loading/Applying for a manually pressurized hand-wand for use in greenhouses, turf (lawns, athletic fields, parks, etc.), rights of way/industrial areas, and foundations/perimeters,
 Mixing/Loading/Applying via mechanically pressurized hand-gun for orchards (in and around trees), greenhouses, turf (golf courses), landscaping and turf (lawns, athletic fields, parks, etc.), industrial/commercial areas, and typical field crops.
 Flagger for typical and high acreage field crops.

Occupational Handler Exposure Data and Assumptions
A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments.  Each assumption and factor is detailed below on an individual basis.

Application Rate:
Maximum application rates were used as noted in Table 4.1.

Unit Exposures:
It is the policy of HED to use the best available data to assess handler exposure.  Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, include PHED 1.1, the AHETF database, September 2015 revision to the Occupational Pesticide Handler Unit Exposure Surrogate Reverence Table, the November 2015 Aquatic Use SOP, the July 2015 Occupational Aquatic Assumptions or other registrant-submitted occupational exposure studies.  Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA.  The standard values recommended for use in predicting handler exposure that are used in this assessment, known as "unit exposures", are outlined in the "Occupational Pesticide Handler Unit Exposure Surrogate Reference Table", which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website.

Area Treated or Amount Handled:
The inputs for area treated were based on information in ExpoSAC Policy 9.1 and based on information received from the Army Corps of Engineers (for the aquatic uses specifically).  The following summarizes the inputs used for estimating handler exposures:

 1200 acres for aerial application to high acreage crops,
 350 acres for aerial application to typical acreage crops and orchards,
 350 acres for flaggers,
 210 acre-feet (30 acres and 7 foot depth) for boom sprayer applications to aquatic areas/lakes/ponds - submersed weeds,
 56 acre-feet (8 acres and 7 foot depth) for boom sprayer applications to aquatic areas/lakes/ponds - surface weeds,
 210 acre-feet (30 acres and 7 foot depth) for aerial applications to aquatic areas/lakes/ponds,
 200 acres for ground application to high acreage crops,
 80 acres for ground application to typical acreage crops,
 40 acres for ground applications to golf courses, ornamental crops and orchards/vineyards,
 5 acres for mechanically pressurized handgun to turf (golf courses, lawns, athletic fields, parks) and landscaping,
 1,125 gallons for injection/spray application to sewer lines,
 1000 gallons for mechanically-pressurized handgun,
 40 gallons for backpack and manually-pressurized handwand applications, and
 2 bottles (32-oz) for Trigger-Spray bottle treatments.

Exposure Duration:
HED classifies exposures from 1 to 30 days as short-term and exposures 30 days to six months as intermediate-term.  Exposure duration is determined by many things, including the exposed population, the use site, the pest pressure triggering the use of the pesticide, and the cultural practices surrounding that use site.  For most agricultural uses, it is reasonable to believe that occupational handlers will not apply the same chemical every day for more than a one-month time frame; however, there may be a large agribusiness and/or commercial applicators who may apply a product over a period of weeks (e.g., completing multiple applications for multiple clients within a region).

For diquat dibromide, based on the registered uses, short-, and intermediate-term exposure(s) are expected for the following reasons: (1) type of application method (aquatic, ground directed defoliant/desiccant), and (2) max number of applications per year (2).

Mitigation/Personal Protective Equipment:
Estimates of dermal and inhalation exposure were calculated for various levels of personal protective equipment (PPE). The diquat dibromide product labels direct mixers, loaders, applicators and other handlers to wear long-sleeved shirt and long pants, coveralls, shoes plus socks, chemical-resistant gloves and protective eyewear such as goggles or face shield, chemical-resistant headgear for overhead exposure, chemical resistant apron when cleaning equipment and  no respirator. However, for sewer line treatments, a dust/mist respirator (TC-21C) is required as well.

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations
The algorithms used to estimate non-cancer exposure and dose for occupational handlers can be found in Appendix A.

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates
The occupational handler non-cancer exposure and risk estimates for diquat dibromide are summarized in Table 6.1.1. There are no dermal short- or intermediate-term occupational risk estimates of concern at label specific PPE associated with the existing uses of diquat dibromide (i.e., MOEs >= 100).  Some occupational scenarios reached acceptable inhalation MOEs at baseline/label specific PPE (i.e., no respirator); however, several exposure scenarios presented risk estimates of concern (MOE < 30) at baseline/label specific PPE.

The following scenarios reached acceptable MOEs with the addition of a PF5 respirator:
 Mixing/Loading for aerial applications to typical field crops,
 Mixing/Loading for boom sprayer applications to aquatic areas (surface weeds),
 Mixing/Loading for groundboom applications to high acreage crops,
 Applying with groundboom to typical and high acreage field crops.
 Mixing/Loading/Applying for a backpack sprayer to rights of way and landscaping, turf/athletic fields, structural and industrial/commercial areas,
 Mixing/Loading/Applying for a mechanically-pressurized hand-wand application for the use on greenhouse ornamentals, roses, cut flowers landscaping turf, industrial and commercial areas including foundations, structural and aquatic areas.

The following scenarios reached acceptable MOEs with the addition of a PF10 respirator:
 Applying boom sprayer to aquatic areas (surface weeds),
 Applying mechanically pressurized handgun to rights of way, utilities, railroad, and roadways,
 Flagger for typical and high acreage field crops, and
 Mixing/Loading/Applying for a mechanically-pressurized hand-gun application for use in orchards (in and around trees), industrial/commercial areas, and typical field crops.
The following scenarios do not reach acceptable MOEs even with maximum PPE and EC:
 Mixing/Loading for aerial applications to high acreage crops and aquatic areas,
 Mixer/Loader for boom sprayer applications to aquatic areas (submersed weeds) and
 Mixing/Loading/Applying for a mechanically-pressurized hand-gun application in greenhouses.

Flagger/Aerial Application:
The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for human flaggers where appropriate, agricultural aviation has changed dramatically over the past two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily from the mid 1990's. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990's to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sources to best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.  HED has no data to assess exposures to pilots using open cockpits.  The only data available is for exposure to pilots in enclosed cockpits.  Therefore, risks to pilots are assessed using the engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, and socks); per the Agency's Worker Protection Standard stipulations for engineering controls, pilots are not required to wear protective gloves for the duration of the application. With this level of protection, there are no risk estimates of concern for applicators.

Table 6.1.1.  Occupational Handler Non-Cancer Exposure and Risk Estimates for Diquat Dibromide.
                               Exposure Scenario
                                     Crop
                                      or
                                    Target
                                    Dermal
                                     Unit
                                   Exposure
                                (μg/lb ai)[1]
                                Inhalation Unit
                            Exposure (μg/lb ai)[1]
                                     Max.
                                     App.
                                    Rate[2]
                                Area Treated /
                        Amount Handled Daily[3] (acres)
                                    Dermal
                                  Inhalation

                                  Mitigation
                                     Level
                               Mitigation Level

                              Dose (mg/kg/day)[4]
                                    MOE[5]
                                   LOC = 100
                              Dose (mg/kg/day)[6]
                                    MOE[7]
                                   LOC = 30
                               Mixer/Loader (SC)

                                    Aerial

                                Field crop/[8]
                                    typical
                                   Label[10]
                                     29.1
                                     Label
                                     0.219
                                0.5 lb ai/acre
                                      350
                                    0.00019
                                    16,000
                                     Label
                                    0.00048
                                      8.8

                                Mitigation PF 5
                                    0.0438

                                  Mitigation
                                     PF 5
                                   0.000096
                                      44

         Field crop, high-acreage                            (Canola/
                                   Potato -
                                 pre-harvest)

                                     Label
                                     0.219

                                     1,200
                                    0.00066
                                     4,600
                                     Label
                                    0.0016
                                      2.6

                                Mitigation PF 5
                                    0.0438

                                  Mitigation
                                      PF 5
                                    0.00033
                                      13

                               Mitigation PF 10
                                    0.0219

                                  Mitigation
                                     PF 10
                                    0.00016
                                      26

                                      EC
                                     0.083

                                      EC
                                      6.7
                                    Aerial
                                 Aquatic Areas
                                     Label
                                     29.1
                                     Label
                                     0.219
                               4 lb ai/Acre-feet
                                     210
                                   acre-feet
                                    0.00092
                                     3,300
                                    0.0023
                                      1.8

                                Mitigation PF 5
                                    0.0438

                                    0.00046
                                      9.1

                               Mitigation PF 10
                                    0.0219

                                    0.00023
                                      18

                                      EC
                                     0.083

                                   0.000871
                                      4.8
                                 Boom Sprayer
                      Aquatic areas[9] (Submersed Weeds)

                                     Label
                                     29.1

                                     Label
                                     29.1

                                     Label
                                     29.1
                                     Label
                                     0.219
                               4 lb ai/Acre-feet
                                     210
                                  acre-feet

                                    0.00092

                                     3,300

                                     Label
                                    0.0023
                                      1.8

                                Mitigation PF 5
                                    0.0438

                                  Mitigation
                                     PF 5
                                    0.00046
                                      9.1

                               Mitigation PF 10
                                    0.0219

                                  Mitigation
                                     PF 10
                                    0.00023
                                      18

                                      EC
                                     0.083

                                      EC
                                    0.00087
                                      4.8
                                 Boom Sprayer
                         Aquatic areas (Surface Weeds)

                                     Label
                                     0.219
                               4 lb ai/Acre-feet
                                      56
                                   acre-feet
                                   0.000245

                                    12,000

                                     Label
                                   0.000614
                                      6.8

                                Mitigation PF 5
                                    0.0438

                                  Mitigation
                                     PF 5
                                   0.000123

                                      34
                           Mechanically Pressurized
                                    Handgun
              Rights-of-way (e.g., utilities, railroad, roadways

                                     Label
                                     0.219

                                 0.1 lb ai/gal
                                     1,000
                                      gal
                                   0.000011
                                    280,000
                                     Label
                                   0.000027
                                      150

                                Sewer Pipes[10]

                                 0.1 lb ai/gal
                                     1,125
                                      gal
                                   0.000012
                                    240,000
                                     Label
                                   0.0000062
                                      680

                                  Groundboom
                     Golf course (tees, (fairways, greens)

                                0.5 lb ai/acre

                                0.5 lb ai/acre
                                      40
                                   0.000022
                                    140,000
                                     Label
                                   0.000055
                                      77

                         Field-grown ornamental crops

                                     Label
                                     0.219

                               Orchard/Vineyard

                                  Groundboom
                              Field crop/ typical

                                      80
                                   0.000044
                                    69,000
                                     Label
                                    0.00011
                                      38

                                  Field crop,
                                 high-acreage

                                     Label
                                     0.219

                                      200
                                    0.00011
                                    28,000
                                     Label
                                    0.00027
                                      15

                                Mitigation PF 5
                                    0.0438

                                  Mitigation
                                     PF 5
                                   0.000055
                                      77
                                  Applicator
                                    Aerial
                              Field crop/Typical
                               Orchard/Vineyard
                                      EC
                                     2.08
                                      EC
                                    0.0049
                                0.5 lb ai/acre
                                      350
                                      EC
                                   0.000014
                                      EC
                                    220,000
                                      EC
                                   0.000011
                                      EC
                                      390

                                  Field crop,
                                 high-acreage

                                     1200
                                      EC
                                   0.000047
                                      EC
                                    64,000
                                      EC
                                   0.000037
                                      EC
                                      110

                      Aquatic areas (lakes, ponds, etc.)
                                      EC
                                     2.08

                               4 lb ai/acre-feet
                                     210
                                   acre-feet
                                      EC
                                   0.000066
                                      EC
                                    46,000
                                      EC
                                   0.000052
                                      EC
                                      82

                                  Groundboom

                     Golf course (fairways, tees, greens),
                         Field-grown ornamental Crops,
                               Orchard/Vineyard

                                     Label
                                     12.6

                                     Label
                                     12.6

                                     Label
                                     0.34

                                0.5 lb ai/acre

                                0.5 lb ai/acre
                                      40
                                   0.0000095
                                    320,000
                                     Label
                                   0.000085

                                      49

                              Field crop, typical

                                     Label
                                     0.34

                                      80
                                   0.000019
                                    160,000
                                     Label
                                    0.00017
                                      25

                                Mitigation PF 5
                                     0.068

                                  Mitigation
                                     PF 5
                                   0.000034
                                      120

                                  Field crop,
                                  high-acreage

                                     Label
                                     0.34

                                      200
                                   0.000047
                                    63,000
                                     Label
                                    0.00043
                                      9.9

                                Mitigation PF 5
                                     0.068

                                  Mitigation
                                     PF 5
                                   0.000085

                                      49

                                 Boom Sprayer
                         Aquatic areas (Surface Weeds)

                                     Label
                                     0.34
                               4 lb ai/acre-feet
                                      56
                                     acre-
                                     feet
                                   0.000106

                                    28,000

                                     Label
                                    0.0036
                                      4.4

                                  Mitigation
                                      PF5
                                     0.068

                                  Mitigation
                                     PF 5
                                    0.00019
                                      22

                                  Mitigation
                                     PF10
                                     0.034

                                  Mitigation
                                     PF 10
                                   0.0000953

                                      44

                           Mechanically Pressurized
                                    Handgun
              Rights-of-way (e.g., utilities, railroad, roadways
                                     Label
                                     1,360

                                     Label
                                     8.68
                                0.01 lb ai/gal
                                     1,000
                                      gal
                                    0.00051

                                     5,900

                                     Label
                                    0.00109
                                     3.9

                                Mitigation PF 5
                                     1.74

                                  Mitigation
                                     PF 5
                                    0.00022
                                      19

                               Mitigation PF 10
                                     0.87

                                  Mitigation
                                     PF 10
                                    0.00011
                                      39
                             Trigger-Spray bottle
                                    (R-T-U)
                                 Foundations/
                                   perimeter
                                     Label
                                     1,110
                                     Label
                                     61.2
                                    0.0025
                                 lb ai/bottle
                                       2
                                    bottles
                                  0.00000021
                                  14,000,000
                                     Label
                                   0.0000038
                                     1,100

            Landscaping, turf (lawns, athletic fields, parks, etc.)

                                 Flagger (SC)
                                    Aerial
                              Field crop/typical/
                                 high-acreage
                                     Label
                                     10.6
                                     Label
                                     0.35
                                     0.5
                                  lb ai/acre
                                      350
                                   0.000070
                                    43,000
                                     Label
                                   0.000766
                                      5.5

                                  Mitigation
                                     PF 5
                                   0.000154
                                      27

                                  Mitigation
                                     PF 10
                                   0.000077
                                      55
                         Mixer/Loader/Applicator (SC)

                                   Backpack
                                    Sprayer

                                   Backpack
                                    Sprayer
                               Orchard/Vineyard
                            (Ground/soil-directed)
                                     Label
                                     4120
                                     Label
                                     2.58

                                     0.01
                                   lb ai/gal

                                    40 gal

                                    40 gal

                                   0.000062
                                    48,000
                                     Label
                                   0.0000129
                                      330

              Rights-of-way (e.g., utilities, railroad, roadways)
                                     Label
                                    16,900
                                     Label
                                     69.1

                                   0.000254
                                    12,000
                                     Label
                                   0.000345
                                      12

                                  Mitigation
                                     PF 5
                                   0.000069
                                      61

            Landscaping, turf (lawns, athletic fields, parks, etc.)
                              Broadcast Treatment
                                     Label
                                    16,900
                                     Label
                                     69.1

                                     0.01
                                   lb ai/gal

                                   0.000254
                                    12,000
                                     Label
                                   0.000345

                                      12

                                  Mitigation
                                     PF 5
                                   0.000069

                                      61

            Landscaping, turf (lawns, athletic fields, parks, etc.)
                                Spot Treatment