                      UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                         WASHINGTON, D.C. 20460      

                                                 	OFFICE OF CHEMICAL SAFETY AND
                                                                                               POLLUTION PREVENTION



MEMORANDUM
 
Date:	         May 15, 2014

SUBJECT:  Bifenazate: Occupational and Residential Exposure/Risk Assessment for Proposed Uses on Herb Subgroup 19A, Fruiting Vegetable Group 8-10, Pome Fruit Group 11-10, and Timothy Grass Forage and Timothy Grass Hay.

PC Code:  000586
DP Barcode: D388802
Decision Nos.:  446177
Registration Nos.: 59639-107
Petition No.:  1E7847
Regulatory Action:  Section 3
Risk Assessment Type:  Single Chemical
Occupational/Residential  Assessment
Case No.:  NA
TXR No.:  NA
CAS No.:  149877-41-8
MRID No.:  NA
40 CFR:  §180.572


FROM: 	Lata Venkateshwara, Environmental Scientist
		Risk Assessment Branch 1
      Health Effects Division (7509P)

THROUGH: 	Kelly M. Lowe, Environmental Scientist
      Charles Smith, Branch Chief
      Risk Assessment Branch 1
		Health Effects Division (7509P)

		and

		Nancy Tsaur, Chemist, ExpoSAC Designated Reviewer
		Shalu Shelat, Industrial Hygienist, ExpoSAC Designated Reviewer
		Exposure Science Advisory Committee (ExpoSAC) / HED

TO:		Barbara Madden, RM 05
		Registration Division (7505P) 

Chemtura Corporation has proposed a Section 3 Registration (PP# 1E7847) for application of bifenazate to Herb Subgroup 19A (except chive and chervil), Fruiting Vegetable Group 8-10, Pome Fruit Group 11-10, and Timothy Grass Forage and Hay.  The Registration Division (RD) requested that the Health Effects Division (HED) conduct an exposure and risk assessment for these proposed uses of bifenazate.  This memorandum assesses occupational and residential exposure and risk from the use of bifenazate on the sites mentioned above.

It is HED policy to use the best available data to assess exposure.  Sources of generic data, used as surrogate data in the absence of chemical-specific data, include the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) database; the Residential SOPs (Gardens and Trees), and the Agricultural Reentry Task Force (ARTF).  Some of these data are proprietary, and subject to the data protection provisions of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).  

This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on August 29, 2013.  



TABLE OF CONTENTS

1.0	Executive Summary	4
2.0	Summary of Conclusions and Data Requirements	6
2.1	Summary of Risk Estimates	6
2.2	Data Deficiencies and Requirements	6
3.0	Hazard Characterization	6
4.0	Proposed Use Profile	9
5.0	Residential Exposure and Risk Estimates	10
5.1	Residential Handler Exposure/Risk Estimates	10
5.2	Residential Post-application Exposure/Risk Estimates	11
5.3 	Residential Risk Estimates for Use in Aggregate Assessments	12
5.4	Spray Drift	13
5.5	Residential Bystander Post-Application Inhalation Exposure	13
6.0	Occupational Exposure and Risk Estimates	14
6.1	Occupational Handler Exposure/ Risk Estimates	14
Appendix A.  Residential Handler and Post-application Algorithms	22
Appendix B.  Summary of Occupational and Residential Non-cancer Algorithms	25
Appendix C.  Summaries of Dislodgeable Foliar Residue Studies and Proposed Use in Assessment	26
1.0	Executive Summary

This document presents an occupational and residential exposure/risk assessment for the proposed application of bifenazate to herb subgroup 19A (except chive and chervil), fruiting vegetable group 8-10, pome fruit group 11-10, and timothy grass forage and hay. 
The proposed uses will not result in residential exposure; however, the currently registered gardens and ornamentals use has been reassessed in this document to reflect updates to HED's 2012 Residential Standard Operating Procedures (SOPs).  The residential exposures have been revised since they will impact the aggregate assessment for bifenazate.

Proposed Use Profile:
Bifenazate is a selective miticide which controls the motile stage of mites either by direct contact or through contact with foliar residues.  The petition submitted by the Registrant includes addition of the fruiting vegetable group 8-10, herbs subgroup 19A (except chive and chervil), and pome fruit group 11-10 to the Acramite[(R)] 50WS product label (EPA Reg. # 400-503).  This product is formulated as a wettable-powder (WP) in water-soluble bags (WSB). Application is proposed at a maximum rate of 0.5 lb ai/A via ground and aerial application. The petition also included addition of timothy forage and hay to the Acramite(R) 4SC product label (EPA Reg. # 400-514).  This product is formulated as a suspension concentrate (flowable).  Application is proposed at a maximum rate of 0.75 lb ai/A via ground and aerial application, and chemigation. The proposed pre-harvest intervals (PHIs) range from 0 to 7 days. 

Hazard Concerns:
HED identified a short- and intermediate-term dermal toxicological endpoint from a prenatal developmental toxicity rat study where the LOAEL is 80 mg/kg/day. An estimated 25% dermal absorption factor was used for calculating a dermal dose estimate.  The short- and intermediate-term inhalation endpoints were derived from the route specific 28-day inhalation study in rats where the NOAEL is 0.030 mg/L.  The inhalation study NOAEL was converted to human equivalent concentrations (HECs; 0.0009 and 0.0039 mg/L for residential and occupational exposures, respectively) and human equivalent doses (HEDs; 0.14 and 0.19 mg/kg/day for residential and occupational exposures, respectively). The level of concern for inhalation exposure is 30 which includes interspecies (3x), and intraspecies (10x) uncertainty factors.  The interspecies factor was reduced from 10x to 3x due to the HEC calculation accounting for pharmacokinetic (not pharmacodynamic) interspecies differences. The level of concern for dermal exposure is 100 which includes interspecies (10x), intraspecies (10x), and FQPA (1x). 

The average adult body weight of 80 kg was used for estimating dermal dose and 80 kg was used for estimating inhalation dose. No evidence of carcinogenicity was seen in the rat and mouse studies and HED classified bifenazate as "not likely" to be a human carcinogen by any relevant route of exposure.

Residential Exposure/Risk:
The proposed uses will not result in residential exposure; however, the currently registered garden and ornamental use has been reassessed in this document to reflect updates to HED's 2012 Residential Standard Operating Procedures (SOPs).  A total aggregated risk index (ARI) approach was used since the levels of concern (LOCs) for dermal exposure (100) and inhalation exposure (30) are different.  The dermal and inhalation exposure risk estimates for residential handlers are not of concern at baseline for all scenarios.  All the ARIs are above 1 and do not exceed HED's LOC for all scenarios.  All adult and children (6 to 11 years) dermal post-application risk estimates for exposure to treated trees and gardens are not of concern (margins of exposure or MOEs) >= 100).  

Occupational Handler Exposure:
Occupational handler short- and intermediate-term exposure is anticipated from the proposed uses.  Chronic exposure is not expected for the proposed uses. Bifenazate is classified as "not likely to be carcinogenic to humans;" therefore, a cancer assessment was not conducted.  The label for Acramite[(R)]- 50WS only requires protective eyewear, long-sleeved shirt and long pants; shoes and socks.  The label does not require gloves.  The label for Acramite[(R)]- 4SC requires long-sleeved shirt and long pants, shoes plus socks.  It includes a statement that "When not using a closed system, wear apron and chemically resistant gloves made of any waterproof material for mixing/loading activities."

Inhalation risk estimates were not of concern for all scenarios.  MOEs ranged from 100 to 12,000 (MOEs >= 30).  Dermal risk estimates were not of concern for all scenarios.  MOEs ranged from 110 to 33,000 (MOEs >= 100).  All ARIs are greater than 1 except for the following scenarios that require single layer of gloves:
   * Mixing/loading liquids for aerial and chemigation applications and 
   * Mixing/loading/application of liquids via mechanically pressurized handgun (foliar). 

Occupational Post-application Exposure:
Post-application dermal exposure will occur since bifenazate is applied post-emergence as a foliar spray. Chemical-specific DFR data were available and used for bifenazate.   The short- and intermediate-term risk estimates are not of concern (i.e., (MOEs>=100)) on the day of treatment (i.e., Day 0) for the post-application exposure activities.  Based on the Agency's current practices, a quantitative occupational post-application inhalation exposure assessment was not performed for bifenazate 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 bifenazate.

 The 12-hour REI listed on the label is adequate to protect agricultural workers from post-application exposures to bifenazate. 

Review of Human Research
This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical.  These data, which include Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force (ORETF) database; and the Residential SOPs (Gardens/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	Summary of Conclusions and Data Requirements
2.1	Summary of Risk Estimates

Residential Risk Estimate Summary:
The dermal and inhalation exposure risk estimates for residential handlers are not of concern at baseline for all scenarios.   All adult and children (6<11 years) dermal post-application risk estimates for exposure to treated trees and treated gardens are not of concern (MOEs >= 100).  

Occupational Risk Estimate Summary:
Occupational handler inhalation and dermal risk estimates were not of concern for all scenarios.  

The interim Worker Protection Standard (WPS) restricted-entry interval (REI) of 12 hours is adequate to protect agricultural workers.  

2.2	Data Deficiencies and Requirements

There are no data deficiencies or data requirements for the proposed new use of bifenazate.

3.0	Hazard Characterization

The acute toxicity data for bifenazate is summarized below in Table 3.1.  

Table 3.1 Acute Toxicity of Bifenazate.
                                   Guideline
                                      No.
                                  Study Type
                                    MRID #
                                    Results
                               Toxicity Category
                                   870.1100
                                  Acute Oral
                                   44464934
                             LD50 > 5,000 mg/kg
                                      IV
                                   870.1200
                                 Acute Dermal
                                   44464936
                             LD50 > 5000 mg/kg
                                      IV
                                   870.1300
                               Acute Inhalation
                                   44464937
                              LC50 > 4.4 mg/L
                                      IV
                                   870.2400
                            Primary Eye  Irritation
                                   44464938
                               slight irritation
                                      IV
                                   870.2500
                            Primary Skin Irritation
                                   44464939
                               slight irritation
                                      IV
                                   870.2600
                             Dermal Sensitization
                                   45385101
                               dermal sensitizer
                               Magnusson/Kligman
                                   870.2600
                             Dermal Sensitization
                                   44464940
                            not a dermal sensitizer
                                    Buehler


Toxicological doses selected for use in this assessment are summarized in Tables 3.2 and 3.3.  

The short- and intermediate-term dermal endpoints were derived from the 21-day dermal rat study where the NOAEL is 80 mg/kg/day.  The LOAEL is 400 mg/kg/day based upon decreased body weight in females, decreased food consumption in both sexes, increased urinary ketones, increased urinary protein, increased urinary specific gravity, and decreased urinary volume in both sexes, and increased incidences of extramedullary hematopoiesis in the spleen in both sexes.  The level of concern is 100 based upon a 10x-UF for inter-species extrapolations, and a 10x-UF for intra-species variations.  This study protects for the early resorptions in the developmental rat study where the maternal and fetal effects occur at the same dose.  This study is appropriate for the route as well as the durations of exposure, in both residential and occupational settings..  

The short- and intermediate-term inhalation endpoints were derived from the route-specific 28-day inhalation study in rats where the NOAEL is 0.030 mg/L.  The LOAEL is 0.075 mg/L for both sexes based on dried red material around the nose in females, lower body weights and weight gains, decreased food consumption, decreased heart and thymus weights in females, increased incidences of mild brown pigmentation of the spleen, and minimal to mild degeneration of the olfactory epithelium within nasal levels III, IV, and V in both sexes.   This study is appropriate for the route and duration of exposure, and is protective of adults in occupational and residential settings.

The methods and dosimetry equations described in EPA's RfC guidance (1994) are suited for calculating HECs based on the inhalation toxicity NOAEL for use in MOE calculations.  The regional deposited-dose ratio (RDDR), which accounts for the particulate diameter (mass median aerodynamic diameter [MMAD] and geometric standard deviation [g] of aerosols), can be used to estimate the different dose fractions deposited along the respiratory tract.  The RDDR is also based on interspecies differences in ventilation and respiratory-tract surface areas.  Thus, the RDDR can be used to adjust an observed inhalation particulate exposure of an animal to the predicted inhalation exposure for a human.  For the 4-week inhalation study with bifenazate, an RDDR was estimated at 2.8 based on the reported mass medium aerodynamic diameter (MMAD) of 2.20 um and standard deviation (g) of 2.78 and the respiratory-tract surface area of the rat relative to the human.  Since the rat inhalation study was carried out for 6 hr/day for 5 days/week, the only exposure adjustment made was in the assumption of 8 hrs/day for human occupational exposures.  The resulting HECs are 0.0009 mg/L and 0.0039 mg/L for residential and occupational exposures, respectively.  The resulting HEDs are 0.14 and 0.19 mg/kg/day for residential and occupational exposures, respectively.  

The level of concern for inhalation is 30 which includes interspecies (3x) and intraspecies (10x) uncertainty factors.  The interspecies factor was reduced from 10x to 3x due to the HEC calculation accounting for pharmacokinetic (not pharmacodynamic) interspecies differences.  The level of concern for dermal exposure is 100 which includes interspecies (10x), intraspecies (10x), and FQPA (1x). 

The average adult body weight of 80 was used for estimating dermal dose and 80 kg was used for estimating inhalation dose. No evidence of carcinogenicity was seen in the rat and mouse studies and HED classified bifenazate as "not likely" to be a human carcinogen by any relevant route of exposure.  


Table 3.2.  Summary of Toxicological Doses and Endpoints for Bifenazate for Use in Dietary and Non-Occupational Human-Health Risk Assessments.
                              Exposure/ Scenario
                                      POD
                             Uncertainty/FQPA SFs
                RfD, PAD, Level of Concern for Risk Assessment
                        Study and Toxicological Effects
Incidental Oral Short Term (1 - 30 days) and Intermediate Term
NOAEL = 0.9 mg/kg/day
                                   UFA = 10x
                                   UFH = 10x
                                 FQPA SF = 1x
Residential LOC for MOE = 100
90-Day Subchronic- Dogs
LOAEL = 10.4 mg/kg/day based upon changes in hematological parameters in both sexes, increased bilirubin in the urine in males, increased absolute and relative liver weight in females and liver histopathological effects in both sexes.
Dermal Short- and Intermediate-Term (1-30 days and 1-6 months)
LOAEL = 80 mg/kg/day
                                   UFA = 10x
                                   UFH = 10x
                                 FQPA SF = 1x
Residential LOC for MOE = 100
21-Day Dermal Toxicity-Rat
LOAEL = 400 mg/kg/day based on decreased body weight in females, decreased food consumption in both sexes, increased urinary ketones, increased urinary protein, increased urinary specific gravity, and decreased urinary volume in both sexes, and increased incidence of extramedullary hematopoiesis in the spleen in both sexes.
Inhalation Short- and Intermediate-Term (1-30 days, and 1-6 months)
Rat NOAEL = 0.03 mg/L 
                                   UFA = 3x
                                   UFH = 10x
                                 FQPA SF = 1x
                         Residential LOC for MOE = 30
28-Day Inhalation Toxicity-Rat
LOAEL = 0.075 mg/L [M/F] on dried red material around the nose in females, lower body weights and body-weight gains, decreased food consumption, decreased heart and thymus weights in females, increased incidences of mild brown pigmentation of the spleen, and minimal to mild degeneration of the olfactory epithelium within nasal levels III, IV, and V.

HEC= 0.0009 mg/L
HED = 0.14 mg/kg bw/day



Cancer (oral, dermal, inhalation)
Bifenazate is classified as "not likely to be a human carcinogen".
Point of departure (POD) = a data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no-observed adverse-effect level.  LOAEL = lowest-observed adverse-effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor.  PAD = population-adjusted dose (a = acute, c = chronic).  RfD = reference dose.  MOE = margin of exposure.  LOC = level of concern.  N/A = not applicable.


Table 3.3 Summary of Toxicological Doses and Endpoints for Bifenazate for Use in Occupational Human Health Risk Assessments
                              Exposure/ Scenario
                                      POD
                              Uncertainty Factors
                     Level of Concern for Risk Assessment
                        Study and Toxicological Effects
Dermal Short- and Intermediate-Term (1-30 days and 1-6 months)
LOAEL = 80 mg/kg/day 
                                   UFA = 10x
                                   UFH = 10x
                                       
Occupational LOC for MOE = 100
21-Day Dermal Toxicity- Rat
LOAEL = 400 mg/kg/day based on decreased body weight in females, decreased food consumption in both sexes, increased urinary ketones, increased urinary protein, increased urinary specific gravity, and decreased urinary volume in both sexes, and increased incidence of extramedullary hematopoiesis in the spleen in both sexes.
Inhalation Short- and Intermediate-Term (1-30 days, and 1-6 months)
Rat NOAEL = 0.03 mg/L 
                                   UFA = 3x
                                       
                                   UFH = 10x
                                       
Occupational LOC for MOE = 30
28-Day Inhalation Toxicity-Rat
LOAEL = 0.075 mg/L [M/F] based on dried red material around the nose, lower body weights and body-weight gains, decreased food consumption, mild brown pigmentation of the spleen, and minimal to mild degeneration of the olfactory epithelium within nasal levels III, IV, and V in both sexes.

HEC = 0.0039 mg/L
HED = 0.19 mg/kg bw/day



Cancer (oral, dermal, inhalation)
Bifenazate is classified as "not likely" to be a human carcinogen.
POD = a data point or an estimated point that is derived from observed dose-response data and  used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.  NOAEL = no-observed adverse-effect level.  LOAEL = lowest-observed adverse-effect level.  UF = uncertainty factor.  UFA = extrapolation from animal to human (interspecies).  UFH = potential variation in sensitivity among members of the human population (intraspecies).  MOE = margin of exposure.  LOC = level of concern.  

4.0	Proposed Use Profile

Table 4.1 provides a summary of the proposed use patterns. Acramite[(R)] 50WS is formulated as a wettable-powder (WP) in water-soluble bags (WSB). It is proposed for use on fruiting vegetable group 8-10, herbs subgroup 19A (except chive and chervil), and pome fruit group 11-10 at a maximum application rate of 0.5 lb ai/A via ground and aerial application. Acramite(R) 4SC is formulated as a suspension concentrate (flowable) and is proposed for use on timothy forage and hay at a maximum application rate of 0.75 lb ai/A via ground and aerial application, and chemigation. 

The proposed pre-harvest intervals (PHIs) range from 0 to 7 days. The Acramite(R) 4SC label requires applicators and other handlers to wear a long-sleeved shirt and long pants and shoes plus socks, plus an apron and chemical-resistant gloves of any waterproof material for mixing/loading activities (when not using a closed system). The Acramite(R) 50WS label requires applicators and other handlers to wear protective eyewear, long-sleeved shirt and long pants, and shoes plus socks.  The label does not require gloves.


Table 4.1. Summary of Proposed Directions for Use of Bifenazate.
Commodity
Trade Name (EPA Reg. No.)
Application Timing, Type, Equipment
Application Rate
(lb ai/A)
Maximum Seasonal Application Rate
(lb ai/A)
PHI
(days)
Maximum Number Applications

Min. GPA
                  Herbs subgroup 19A (except chives, chervil)
                           Acramite(R) 50WS (400-503)
                                  Groundboom
                                    Aerial
                                   Airblast
                                   Handheld
                                      0.5
                                      0.5
                                       3
                                       1
                                  50 (ground)
                         Fruiting vegetable group 8-10
                                       
                                       
                                       
                                       
                                       3
                                       
                                 50 (ground);
                                   10 (air)
                            Pome fruit group 11-10
                                       
                                       
                                       
                                       
                                       7
                                       
                                      50
                                   (ground)
                           Timothy forage and hay[1]
                                Acramite(R) 4SC
                                   (400-514)
                                  Groundboom
                                  Chemigation
                                    Aerial
                                   Handheld
                                     0.75
                                     0.75
                                  0 (forage)
                                       
                                      20
                                   (ground);
                                   10 (air)





7 (hay)


PHI = pre-harvest interval
GPA = gallons of water per acre
1  Application can only be made in Eureka and Humboldt Counties in Nevada


5.0	Residential Exposure and Risk Estimates

 The proposed uses do not involve applications by homeowners or commercial applicators in residential settings.  Therefore, no new residential exposure is expected.  However, there are existing residential uses that have been reassessed in this document to reflect updates to HED's 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html) along with policy changes for body weight assumptions.  The revision of residential exposure estimates will impact the human health aggregate risk assessment for bifenazate.

5.1	Residential Handler Exposure/Risk Estimates

The residential handler exposure assessment estimates dermal and inhalation exposures for individuals using bifenazate on residential ornamentals.  The quantitative exposure/risk assessment developed for residential handlers is based on the following scenarios: 
		
(1) mixing/loading/applying liquids with manually-pressurized hand wand,  
(2) mixing/loading/applying liquids with hose-end sprayer,
(3) mixing/loading/applying liquids with backpack, and
(4) mixing/loading/applying liquids with sprinkler can.

Unit exposure values and estimates for area treated were taken from HED's 2012 Residential SOPs:  Gardens and Trees. 

Combining Exposures/Risk Estimates:
A total aggregated risk index (ARI) was used since the LOCs for dermal exposure (100) and inhalation exposure (30) are different.  The target ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern.  The aggregate risk index (ARI) was calculated as follows.

Aggregate Risk Index (ARI) = 1/ [(Dermal LOC / Dermal MOE) + (Inhalation LOC / Inhalation MOE)]

Short-term risk estimates for residential handlers are presented in Table 5.1.  Intermediate-term exposures are not likely because of the intermittent nature of applications by homeowners.  Short-term dermal and inhalation risk estimates to residential handlers do not exceed HED's level of concern for all scenarios.  All the ARIs are above 1 and do not exceed HED's level of concern for all scenarios.

Table 5.1.  Residential Handler Exposure and Risk Estimates for Bifenazate Applications to Ornamentals.
                               Exposure Scenario
                              Application Rate[1]
                             Area Treated Daily[2]
                      Baseline Unit Exposures (mg/lb ai)
                         Baseline Dose[4] (mg/kg/day)
                                  Baseline MOE5
Total
                                       
                                       
                                       
                                   Dermal[3]
                                 Inhalation[3]
                                    Dermal
                                  Inhalation
                                    Dermal
                                  (LOC = 100)
                             Inhalation (LOC = 30)
                                    ARI[6]
          Mixer/Loader/Applicator for Soluble Concentrates( Liquids)
                                       
Manually-pressurized handwand
                               0.00125 lb ai/gal
                                     5 gal
                                      63
                                     0.018
                                    0.0049
                                   0.0000014
                                    16,000
                                    100,000
                                      150
                               Hose-end sprayer
                               0.00125 lb ai/gal
                                    11 gal
                                      58
                                    0.0014
                                     0.01
                                  0.00000024
                                     8,000
                                    580,000
                                      80
                                   Backpack
                               0.00125 lb ai/gal
                                     5 gal
                                      130
                                     0.14
                                     0.01
                                   0.000011
                                     7,900
                                    13,000
                                      66
                                 Sprinkler can
                               0.00125 lb ai/gal
                                     5 gal
                                      58
                                    0.0014
                                    0.0045
                                  0.00000011
                                    18,000
                                   1,300,000
                                      180
1. Application rates based on communication between the Registrant and EPA regarding the maximum rates allowed on the labels for the residential use sites.  From label 400-508: 2.0 lb ai/gal/128 fl oz gal *  8 fl oz/100 gal = 0.00125 lb ai/gal
2. Based on HED's SOPs: Gardens and Trees (HED's 2012 Residential SOPs)
3. Baseline Dermal:  Long-sleeve shirt, long pants, shoes and socks and no gloves; Baseline Inhalation: no respirator.  
4. Dose (mg/kg/day) = daily unit exposure (mg/ - lb ai) x application rate (lb ai/gal) x gal treated  x% Absorption (100% dermal and 100% inhalation assumed) / Body weight (80 kg).
5. MOE = NOAEL (Dermal = 80 mg/kg/day; Inhalation = 0.14 mg/kg/day) / daily dose (mg/kg/day).  
6. ARI = Aggregate Risk Index = 1/ [(Dermal LOC / Dermal MOE) + (Inhalation LOC/ Inhalation MOE)].	


5.2	Residential Post-application Exposure/Risk Estimates

Non-cancer Exposure/Risk Estimates
Short-term dermal exposure and risk estimates have been assessed for bifenazate.   The scenarios, routes of exposure and lifestages assessed include:

   * Gardens and Trees:  adults (dermal) and children 6< 11 years old (dermal).

The lifestages (i.e., adults and children 6 < 11 years old) selected for each post-application scenario are based on an analysis provided as an Appendix in the 2012 Residential SOPs.  These lifestages are not the only lifestages that could be potentially exposed for these post-application scenarios; however, the assessment of these lifestages is health protective for the exposures and risks for any other potentially exposed lifestages.  

Residential Post-application Exposure Data and Assumptions
A series of assumptions and exposure factors served as the basis for completing the residential post-application risk assessment.  Each assumption and factor is detailed in the 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

Residential Post-application Non-Cancer Exposure and Risk Equations
The algorithms used to estimate residential post-application exposure and dose can be found in the 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).  For this assessment a DFR value was used.

Table 5.2 lists the updated assessments of currently registered residential post-application exposures and risk estimates.  All adult and children dermal post-application risk estimates for exposure to treated trees and to treated gardens are not of concern (MOEs >= 100.

Table 5.2.  Short- and Intermediate-Term Residential Post-application Exposure and Risk Estimates for Bifenazate.
                              Liquid Formulations
                                   Lifestage
                      Post-application Exposure Scenario
                                    Dose[a]
                                    MOEs[b]
                                  (LOC = 100)
                                     Adult
                                       
                                Garden - sprays
                                       
                                     0.037
                                     2,200
                           Child 6 < 11 years old
                                       
                                     0.025
                                     3,100
                                     Adult
                                Tree  -  sprays
                                    0.0034
                                    23,000
                           Child 6 < 11 years old
                                       
                                    0.0023
                                    34,000
a.  Dermal Dose (mg/kg/day) = DFRt (ug/cm[2]) x 0.001 (mg/ug) x short-term TC (cm[2]/hr) x ET (hr/day) x Dermal Absorption (100%) 
                                          BW (kg) 
b.  Dermal MOE = NOAEL (80  mg/kg/day) / Dermal Dose (mg/kg/day)

Inhalation
Based on the Agency's current practices, a quantitative post-application inhalation exposure assessment was not performed for bifenazate at this time.  However, volatilization of pesticides may be a potential source of post-application inhalation exposure to individuals nearby to pesticide applications.  The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in December 2009.  The Agency received the SAP's final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html).  The Agency is in the process of evaluating the SAP report and may, as appropriate, developing policies and procedures, to identifying the need for and, subsequently, the way to incorporate post-application inhalation exposure into the Agency's risk assessments.  If new policies or procedures are put into place, the Agency may revisit the need for a quantitative post-application inhalation exposure assessment for bifenazate.

5.3 	Residential Risk Estimates for Use in Aggregate Assessments 

Table 5.3 reflects the residential risk estimates that are recommended for use in the aggregate assessment for bifenazate.     
   * The recommended residential exposure for use in the adult aggregate assessment reflects dermal post-application exposure to treated gardens.
   * The recommended residential exposure for use in the children 6 to 11 years old aggregate assessment reflects dermal post-application exposure to treated gardens.  
      
Table 5.3.  Short-Term Residential Exposures for the Bifenazate Combined Residential Risk Calculations.
                                  Population
                        Handler Exposure (mg/kg/day)[1]
                   Post-application Exposure (mg/kg/day)[2]
      Recommended Post-application Exposure for Aggregate (mg/kg/day)[3]
                                       
                                    Dermal
                                  Inhalation
                                    Dermal
                                  Inhalation
                                     Oral
                                       
Adult 
                                    0.0045
                                   0.000011
                                     0.037
                                      N/A
                                      N/A
                                     0.037
Children 6 < 11 yrs old
                                      N/A
                                      N/A
                                     0.025
                                      N/A
                                      N/A
                                     0.025
1.  Handler exposure represents high-end handler exposure, where the appropriate duration is appropriate to assess. 
2.  Postapplication exposure represents high-end dermal, inhalation and/or incidental oral exposure for the relevant exposure duration.
3.  The highest estimated total residential exposure (for adults and child populations) should be used as the basis of the aggregate assessments.

5.4	Spray Drift
      
Spray drift is a potential source of exposure to those nearby pesticide applications.  This is particularly the case with aerial application, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundboom and airblast) employed for bifenazate.  The Agency has been working with the Spray Drift Task Force (a task force composed of various registrants which was developed as a result of a Data Call-In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency's Spray Drift website for more information).   The Agency is also taking means to qualitatively and qualitatively address spray drift as a potential source of exposure in risk assessments for pesticides through existing programs such as Ag Drift and chemical specific properties of pesticides.  The potential for spray drift will be quantitatively evaluated for each pesticide during the Registration Review process which ensures that all uses for that pesticide will be considered concurrently. 
 
5.5	Residential Bystander Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure assessment was not performed for bifenazate at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure (<1 x 10[-7] mm Hg @ 25°), and the low proposed use rate (0.75 lb ai/A ).  However, 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 is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post-application inhalation exposure into the Agency's risk assessments.  If new policies or procedures are developed, the Agency may revisit the need for a quantitative post-application inhalation exposure assessment for bifenazate. 

6.0	Occupational Exposure and Risk Estimates

The proposed uses are on agricultural crops; therefore, there is potential for occupational handler and post-application exposure. 

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, current labeling, and types of equipment that can potentially be used, occupational handler exposure is expected from the proposed uses.  The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios:
 
Mixer/Loader:
   1. mixing/loading water soluble bags (engineering controls for the wettable powder scenario) for aerial application; 
   2. mixing/loading water soluble bags (engineering controls for the wettable powder scenario) for groundboom application;
   3. mixing/loading water soluble bags (engineering controls for the wettable powder scenario) for airblast application;
   4.  open mixing/loading liquids for aerial application;
   5. open mixing/loading liquids for groundboom application; 
   6. open mixing/loading liquids for chemigaton;
       
Applicator:
   7. application of sprays via aerial application;
   8. application of sprays via groundboom equipment; 
   9. application of sprays via airblast application; 
   10. application of sprays via chemigation; 

Mixer/Loader/Applicator:
   11. application of  liquids via mechanically pressurized handgun (foliar);
   12. application of wettable powder in water soluble bags via mechanically pressurized handgun (foliar); and

Flagger:
   13. flagging to support aerial spray applications.

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 applications rates as provided in Table 4.1 were used in the assessment.  

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 the Pesticide Handlers Exposure Database (PHED 1.1), the Agricultural Handlers Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) database, 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/Amount Treated:
Based on HED ExpoSAC Standard Operating Policy (SOP) No. 9.1, the area treated in a day was assumed to be:
*       80 acres for groundboom applications,
*       350 acres for aerial and chemigation applications,
*       40 acres for airblast applications, and
*       350 acres for flagging to support aerial treatment.  

Body Weight:
The average adult body weight of 80 kg was used for estimating dermal dose because the selected toxicological PODs are based on developmental effects.  The average adult body weight of 80 kg was used for estimating inhalation dose because the selected toxicological PODs are not based on developmental effects.  

Exposure Duration: 
HED classifies exposures from 1 to 30 days as short-term and exposures and 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 commercial pest control, 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, commercial applicators may apply a product over a period of weeks.  Long-term exposure is not expected.

Note, according to the label there is a maximum of 1 spray per season at a maximum rate of 0.5 lb ai/ A for herbs subgroup 19A, fruiting vegetable groups 8-10 and pome fruit group 11-10 and 0.75 lb ai/A for timothy forage and hay.  Long-term exposures are not expected; therefore, a long-term assessment was not conducted.  

Mitigation Approaches:
For pesticide handlers, it is HED's standard practice to present estimates of dermal exposure for "baseline" that is, for workers wearing a single layer of work clothing consisting of a long sleeved shirt, long pants, shoes plus socks and no protective gloves, as well as for "baseline" and the use of protective gloves or other Personal Protective Equipment (PPE) as might be necessary.  The Acramite(R) 4SC label requires applicators and other handlers to wear a long-sleeved shirt and long pants and shoes plus socks, plus an apron and chemical-resistant gloves for mixing/loading activities (when not using a closed system). The Acramite(R) 50WS label requires applicators and other handlers to wear protective eyewear, long-sleeved shirt and long pants, and shoes plus socks.  The label does not require gloves.

Application Rate:
Refer to the proposed use pattern table in Section 4.0.

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 B.

A total aggregated risk index (ARI) was used since the LOC values for dermal exposure (100) and inhalation exposure (30) are different.  The target ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern.  The aggregate risk index (ARI) was calculated as follows.

Aggregate Risk Index (ARI) = 1/ [(Dermal LOC / Dermal MOE) + (Inhalation LOC / Inhalation MOE)]

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

Table 6.1.1 provides a summary of the estimated exposures and risks to occupational pesticide handlers.  An MOE >= 100 is adequate to protect occupational pesticide handlers from dermal exposures and an MOE >= 30 from inhalation exposures.  Inhalation and dermal risk estimates were not of concern for all scenarios.  All ARIs are greater than 1 and are not risks of concern, except for the following scenarios that require single layer of gloves:
   * Mixing/loading liquids for aerial and chemigation applications and 
   * Mixing/loading/application of liquids via mechanically pressurized handgun (foliar). 


Table 6.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Bifenazate.  
                               Exposure Scenario
                             Dermal Unit Exposure
                                 (ug/lb ai)[1]
                           Inhalation Unit Exposure
                                 (ug/lb ai)[1]
                              Application Rate[2]
                                       
                            Amount Treated Daily[3]
                                       
                             Dose (mg/kg/day)[4,5]
                                   MOE[6,7]
                                     Total
                                       
                                       
                                       
                                       
                                       
                                    Dermal
                                  Inhalation
                                    Dermal
                                  (LOC = 100)
                                  Inhalation
                                  (LOC = 30)
                                    ARI[9]
              Mixer/Loader Wettable Powder in Water Soluble Bags
                                    Aerial 
                                  Application
                               Eng Control[8]: 
                                      9.8
                             Eng Control[8]: 0.24
                                  0.5 lb ai/A
                                     350 A
                                  EC: 0.0215
                                  EC: 0.00053
                                   EC: 3,700
                                    EC: 360
                                    EC: 9.1
                                   Airblast 
                                 Applications
                                       
                                       
                                  0.5 lb ai/A
                                     40 A
                                  EC: 0.00245
                                  EC: 0.00006
                                  EC: 33,000
                                   EC: 3,200
                                    EC: 81
                            Groundboom applications
                                       
                                       
                                  0.5 lb ai/A
                                     80 A
                                  EC: 0.0049
                                  EC: 0.00012
                                  EC: 16,000
                                   EC: 1,600
                                    EC: 40
                             Mixer/Loader Liquids
                                    Aerial 
                                  Application
                                   Base:220
                                  Base: 0.219
                                 0.75 lb ai/A
                                     350 A
                                  Base: 0.723
                                  SL/G: 0.123
                                 Base: 0.00072
                                   Base: 110
                                   SL/G: 650
                                   Base: 260
                                  Base: 0.98
                                   SL/G: 3.7
                                 Chemigation 
                                 Applications
                                       
                                       
                                 0.75 lb ai/A
                                     350 A
                                  Base: 0.723
                                  SL/G: 0.123
                                 Base: 0.00072
                                   Base: 110
                                   SL/G: 650
                                   Base: 260
                                  Base: 0.98
                                   SL/G: 3.7
                            Groundboom applications
                                       
                                       
                                 0.75 lb ai/A
                                     80 A
                                  Base: 0.165
                                 Base: 0.00016
                                   Base: 480
                                  Base: 1,200
                                   Base: 4.3
                                  Applicator
                              Applicator, Aerial 
                                   EC: 2.08
                                  EC: 0.0049
                                 0.75 lb ai/A
                                     350 A
EC: 0.00683
EC: 0.0000161
                                  EC: 12,000
                                  EC: 12,000
                                    EC: 92
                        Applicator, Open Cab Groundboom
                                  Base: 78.6
                                  Base: 0.34
                                 0.75 lb ai/A
                                     80 A
Base: 0.00365
Base: 0.443
                                   Base: 180
                                   Base: 750
                                   Base: 1.3
                        Applicator, Open Cab, Airblast
                                  Base: 1770
                                  Base: 4.71
                                  0.5 lb ai/A
                                     40 A
Base: 0.00383

Base: 0.059
Base: 1,400
                                   Base: 160
                                    Base: 9
                            Mixer/Loader/Applicator
Mixing/Loading Applying Liquids with Mechanically Pressurized Handgun (foliar)
                                  Base: 1,300
                                  SLw/G: 390
                                   Base: 3.9
                              0.0375 lb ai/gallon
                                 1,000 Gallons
                                  Base: 0.61
                                   Base   : 
                                    0.00183
                                   Base: 130
                                   SLw/G:440
                                       
                                   Base: 100
                                       
                                  Base: 0.94
                                  SLw/G: 1.9
                                       
Mixing/Loading Applying Water Soluble Packets with Mechanically Pressurized Handgun (foliar)
                                  Base: 1,300
                                   Base: 3.9
                               0.01 lb ai/gallon
                                 1,000 Gallons
                                  Base: 0.163
                                     Base:
                                   0.000488
                                   Base: 490
                                   Base: 390
                                   Base: 3.6
                                    Flagger
                                    Flagger
                                    Base: 
                                      11
                                  Base: 0.35
                                 0.75 lb ai/A
                                     350 A
                                 Base: 0.0361
                                 Base: 0.0011
                                  Base: 2,200
                                   Base: 170
                                   Base: 4.5

1 Based on "Occupational Pesticide Handler Unit Exposure Surrogate Reference Table" (March 2013); includes data from PHED /AHETF (level of mitigation: Baseline, PPE, Eng. Controls).: 
  Base = single layer and no gloves; no respirator; SL w/G = single layer w/glove; EC = Engineering control; PF5 = dust/mist respirator.
2 Based on proposed labels for bifenazate (see Table 4.1).
3 Exposure Science Advisory Council Policy #9.1.
4 Dermal Dose = Dermal Unit Exposure (ug/lb ai) x CF (0.001 mg/ug) x Application Rate (lb ai/acre) x Area Treated (A/day) x% Absorption (100% dermal) / Body weight (80 kg).
5 Dermal MOE = Dermal NOAEL (80 mg/kg/day)/Dermal Dose (mg/kg/day).
6 Inhalation Dose = Inhalation Unit Exposure (ug/lb ai) x CF (0.001 mg/ug) x Application Rate (lb ai/acre) x Area Treated (A/day) /BW (80 kg). 
7 Inhalation MOE = Inhalation NOAEL (0.19  mg/kg/day)/ Inhalation Dose (mg/kg/day).
8 Engineering controls for the wettable-powder scenario.
9 ARI = Aggregate Risk Index = 1/ [(Dermal LOC / Dermal MOE) + (Inhalation LOC / Inhalation MOE)].

6.2	Post-application Exposure/ Risk

Dermal

HED expects that post-application dermal exposure will occur since bifenazate is applied post-emergence as a foliar spray to upper and lower leaf surfaces. Post-application exposure is expected to be short- and intermediate-term based on information provided on proposed labels (e.g., according to the label there is a maximum of 1 spray per season at a maximum rate of 0.75 lb ai/A).  Only short-term exposure was assessed, however the assessment is protective of intermediate-term exposures since the dermal endpoints are the same.    

Data and Assumptions for Post-application Exposure Scenarios 
It is the policy of HED to use the best available data to assess post-application exposure.  Sources of generic post-application data, used as surrogate data in the absence of chemical-specific data, are derived from Agricultural Reentry Task Force (ARTF) exposure monitoring studies, and, as proprietary data, are subject to the data protection provisions of FIFRA.  The standard values recommended for use in predicting post-application exposure that are used in this assessment, known as "transfer coefficients",  are presented in the "Science Advisory Council for Exposure (ExpoSAC) Policy 3" (http://www.epa.gov/pesticides/science/exposac_policy3.pdf), which, along with additional information about the ARTF data, can be found at http://www.epa.gov/pesticides/science/post-app-exposure-data.html.  Table 9 provides a summary of the transfer coefficients and activities associated with Herb Subgroup 19A (except chive and chervil), Fruiting Vegetable Group 8-10, Pome Fruit Group 11-10, and Timothy Grass Forage and Timothy Grass Hay. 

Table 6.2.1 summarizes the possible scenarios. In addition, the following assumptions were used in the calculations:

 Exposure Duration: 8 hours per day
 Body Weight: 80 kg for dermal and 80 kg for inhalation
 
 Table 6.2.1. Anticipated Post-application Activities and Dermal Transfer Coefficients.
 Proposed Crops
                           Policy Crop Group Category
                                Application Rate
                                  (lb ai/acre)
                        Transfer Coefficients (cm[2]/hr)
                                   Activities
                              Fruiting vegetable 
                                   group 8-10
                              Vegetable, fruiting
                                      0.5
                                     1,900
                             Irrigation (hand-set)
                                        
                                        
                                        
                                     1,100
                       Harvesting (hand), tying/training
                                        
                                        
                                        
                                      550
                       Harvesting (hand), tying/training
                                        
                                        
                                        
                                      230
                                 Transplanting
                                        
                                        
                                        
                                      210
                                   Scouting
                                        
                                        
                                        
                                       90
                Hand pruning, scouting, hand weeding, thinning
                  Herbs subgroup 19A (except chives, chervil)
                               Vegetable, leafy*
                                      0.5
                                     1,900
                             Irrigation (hand-set)
                                        
                                        
                                        
                                     1,400
                                Hand harvesting
                                        
                                        
                                        
                                      230
                                 Transplanting
                                        
                                        
                                        
                                      210
                                   Scouting
                                        
                                        
                                        
                                       70
                            Hand weeding, thinning
                             Pome fruit group 11-10
                          Tree, "fruit," deciduous
                                      0.5
                                     3,600
                                   Thinning 
                                        
                                        
                                        
                                     1,400
                                Hand harvesting
                                        
                                        
                                        
                                      580
                       Scouting, hand pruning, training
                                        
                                        
                                        
                                      230
                                 Transplanting
                                        
                                        
                                        
                                      100
           Hand weeding, propping, orchard maintenance, bird control
                            Timothy forage and hay 
                           Field/row crop, low/medium
                                      0.75
                                     1,900
                             Irrigation (hand-set)
                                        
                                        
                                        
                                     1,100
                                   Scouting
                                        
                                        
                                        
                                      210
                                   Scouting
                                        
                                        
                                        
                                       70
                            Hand weeding, thinning
*Activities and transfer coefficients associated with parsley considered to be representative for new use site. 

Chemical-specific DFR data were available for bifenazate; however, the data were not for the currently proposed crops.  Since DFR data are not available for the specific crops currently proposed for bifenazate, the available data were used as surrogates.  Based on a review of the available data, it was decided that the DFR data for Spathiphyllum (Peace Lily) in greenhouses would be used as a surrogate for the proposed field crops (fruiting vegetable group 8-10, herb subgroup 19 A, pome fruit group 11-10, and timothy forage and hay).  

Even though the data are not for the specific crops, it is the only chemical-specific data submitted to HED.  There are several limitations that were considered such as (1) the study represents DFR data collected in a greenhouse which may potentially be a more conservative estimate of residue dissipation compared to field crops, (2) the formulation in the study is a wettable powder packaged in a water soluble bag whereas one of the proposed labels (EPA Reg.#400-514) is for a product that is a suspension concentrate (liquid), (3) the application rate was lower in the study (0.29 lb ai/A) compared to the proposed labels (0.5 lb ai/A and 0.75 lb ai/A), and (4) the application was made with a calibrated hand-held boom sprayer.  

Tables 6.2.2 provide a summary of the data for use in the post-application exposure and risk calculations.  Appendix C provides summaries of the studies and references.  

Table 6.2.2.  Summary of DFR Values and Regression Analysis Results for Treated Spathiphyllum (Peace Lily) in Greenhouses with Bifenazate (MRID# 448597-01).
                                Input/Parameter
                                 Site: Florida
                                  Bifenazate
Application Rate (lb ai/A) [a] Study Target Rate = 0.29 lb ai/A
0.29 lb ai/A
Spray Volume (GPA) 
5 gallons/1000 ft[2]
Measured Average Day 0 Residue (ug/cm[2])
0.151
Predicted Day 0 Residue (ug/cm[2]) [b]
0.161
Slope
-0.07
Half-life (days)
9.9
R[2]
0.8433
a.  The application was conducted using hand-held boom sprayer. 
b.  Regressions are based on data collected after second application. 

The following equations were used to calculate risks for workers performing postapplication activities:

Daily Dermal Dose t = (DFRt x CF1 x TC x DA x ET) / BW 

Where:

Daily Dermal Dose	=	Absorbed dose received from exposure to a pesticide in a given scenario on day 					"t" (mg/kg/day),
DFRt 			=	dislodgeable foliage residue on day "t" (ug/cm[2]),
CF1			=	conversion factor (1E-3 mg/ug),
TC			=	transfer coefficient (cm[2]/hr),					
DA			=     	dermal absorption factor (unitless),
ET			=	exposure time (hr/day), and
BW			=	body weight (kg).


MOE = 	Point of Departure (mg/kg/day) / Daily Dermal Dose (mg/kg/day)

HED has determined that short- and intermediate-term risk estimates are not of concern (i.e., MOEs <100) on the day of treatment (i.e., Day 0) for all the post-application exposure activities. Estimates were calculated for the highest transfer coefficients and are protective of all other activities. Table 6.2.3 presents the risk estimates for all crops for the highest transfer coefficient associated with that crop; this represents the activities with the highest estimated risk. 


Table 6.2.3.  Dermal Post-application Exposure and Risk for Bifenazate Using Chemical-Specific DFR Data.
                                     Crop
                               Application  Rate
                                   (lb ai/A)
                Highest Transfer Coefficient for Crop (cm[2]/hr) 
                            and Associated Activity
                               DFR[1] (ug/cm[2])
                             Days After Treatment
                                 Daily Dose[2]
                                    (mg/kg/
                                     day)
                                    MOE3  
                         Fruiting vegetable Group 8-10
                                      0.5
                                     1,900 
                             (irrigation; hand-set)
                                     0.278
                                 0 (12 hours)
                                    0.0528
                                     1,500
                              Herbs Subgroup 19A
                                      0.5
                          1,900 (irrigation; hand-set)
                                     0.278
                                 0 (12 hours)
                                    0.01528
                                     1,500
                            Pome fruit Group 11-10
                                      0.5
                                     3,600
                                (thinning fruit)
                                     0.278
                                 0 (12 hours)
                                     0.10
                                      800
                            Timothy forage and hay
                                     0.75
                                     1,900
                             (irrigation; hand-set)
                                     0.416
                                 0 (12 hours)
                                     0.079
                                     1,000
1.  Chemical-specific DFR = predicted chrysanthemum DFR data for Spathiphyllum (Peace Lily) in greenhouses for a surrogate for the proposed field crops (fruiting vegetable group 8-10, herb subgroup 19 A, pome fruit group 11-10, and  timothy forage and hay).   Application rate in studies is less than the proposed application rate.  
2.  Dermal Dose = [DFR (ug/cm[2]) x TC (cm[2]/hr) x 0.001 mg/ug x 8 hrs/day x DA (100%)]  body-weight (80 kg).
3  MOE = NOAEL (Short- and Intermediate-term NOAEL 80 mg/kg/day)/Daily Dose (LOC=100)).  

Inhalation 
Based on the Agency's current practices, a quantitative occupational post-application inhalation exposure assessment was not performed for bifenazate at this time primarily because it has a low acute inhalation toxicity (Toxicity Category IV), has a low vapor pressure (<1 x 10-7 torr at 25ºC), and is applied at a low use rate (max of  0.75 lb ai/A). However, there are multiple potential sources of post-application inhalation exposure to individuals performing post-application activities in previously treated areas.  These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides.  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 is in the process of evaluating the SAP report as well as available post-application inhalation exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post-application inhalation exposure into the Agency's risk assessments.  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 bifenazate.

REI 
 Bifenazate is classified in acute Toxicity Category IV for acute dermal, inhalation, and oral toxicity, primary eye irritation, and primary skin irritation.    Bifenazate is a dermal sensitizer by the Magnusson/Kligman method, but not the Buehler method.  The 12-hour REI listed on the label is adequate to protect agricultural workers from post-application exposures to bifenazate.



Appendix A.  Residential Handler and Post-application Algorithms

1.0	Residential Handlers
1.1	Residential Handler Exposure Calculations

1.1.1	Turf, Gardens and Trees, Indoor Environments

Dermal and Inhalation Handler Exposure Algorithm
Daily dermal and inhalation exposure (mg/day) for residential pesticide handlers, for a given formulation-application method combination, is estimated by multiplying the formulation-application method-specific unit exposure by an estimate of the amount of active ingredient handled in a day, using the equation below:

                                E = UE * AR * A

where:

E = exposure (mg/day);
UE = unit exposure (mg/lb ai);
AR = application rate (e.g., lb ai/ft[2], lb ai/gal); and
A = area treated or amount handled (e.g., ft[2]/day, gal/day).

1.2	Residential Handler Dose Calculations

Dermal and/or inhalation absorbed doses normalized to body weight are calculated as:
                                       
                                D = E *AF / BW

where:

D = dose (mg/kg-day);
E = exposure (mg/day);
AF = absorption factor (dermal and/or inhalation); and
BW = body weight (kg).

2.0	Residential Post-application
2.1	Gardens and Trees
Post-application Dermal Exposure Algorithm
Exposure resulting from contacting previously treated gardens and trees while performing physical activities is calculated as shown below.  Residential post-application exposure assessment must include calculation of exposure on the day of application.  Therefore, though an assessment can present exposures for any day "t" following the application, it must include "day 0" exposure.

	E = DFRt * CF1 * TC * ET 	

where:

E = exposure (mg/day);
DFRt = dislodgeable foliar residue on day "t" (ug/cm[2]);
CF1 = weight unit conversion factor (0.001 mg/ug);
TC  = transfer coefficient (cm[2]/hr); and
ET  = exposure time (hrs/day).

In the absence of chemical-specific data, DFRt can be calculated as follows:

	DFRt = AR * FAR * (1-FD)t * CF2 * CF3 	

where:

DFRt = dislodgeable foliar residue on day "t" (ug/cm[2]);
AR = application rate (lbs ai/ft[2] or lb ai/acre);
FAR = fraction of ai as dislodgeable residue following application (unitless);
FD = fraction of residue that dissipates daily (unitless);
t = post-application day on which exposure is being assessed;
CF2 = weight unit conversion factor (4.54 x 10[8] ug/lb); and
CF3 = area unit conversion factor (1.08 x 10[-3] ft[2]/cm[2] or 2.47 x 10[-8] acre/cm[2]).

Absorbed dermal dose, normalized to body weight, is calculated as:

	 	
where:
      D	= dose (mg/kg-day);
      E	= exposure (mg/day);
      AF	= absorption factor (dermal and/or inhalation); and
      BW	= body weight (kg).

Table A-X:  Gardens, Trees, and "Pick-your-own" Farms  - Inputs for Residential Post-application Dermal Exposure 
                              Algorithm Notation
                                Exposure Factor
                                    (units)
                               Point Estimate(s)
                                       
                                      AR
                               Application rate
                            (mass ai per unit area)
                                    [input]
                                      FAR
        DFR following application, if chemical-specific is unavailable
                                  (fraction)
                                     0.25
                                      FD
        Daily residue dissipation, if chemical-specific is unavailable
                                  (fraction)
                                     0.10
                                      TC
                             Transfer Coefficient
                                  (cm[2]/hr)
                                  Gardens[a]
                                    Adults
                                     8400
                                       
                                       
                                       
                         Children 6 < 11 years old
                                     4600
                                       
                                       
                    Trees, Retail Plants (if applicable)[a]
                                    Adults
                                     1700
                                       
                                       
                                       
                         Children 6 < 11 years old
                                      930
                                       
                                       
                                 Indoor Plants
                                    Adults
                                      220
                                       
                                       
                                       
                         Children 6 < 11 years old
                                      120
                                      ET
                                 Exposure Time
                                (hours per day)
                              Home activities[b]
                                    Gardens
                                    Adults
                                      2.2
                                       
                                       
                                       
                                       
                         Children 6 < 11 years old
                                      1.1
                                       
                                       
                                       
                     Trees, Retail Plants (if applicable)
                                    Adults
                                      1.0
                                       
                                       
                                       
                                       
                         Children 6 < 11 years old
                                     0.50
                                       
                                       
                                       
                                 Indoor Plants
                                    Adults
                                      1.0
                                       
                                       
                                       
                                       
                         Children 6 < 11 years old
                                     0.50
                                       
                                       
                   "Pick-your-own" Farms (if applicable)
                                    Adults
                                      5.0
                                       
                                       
                                       
                         Children 6 < 11 years old
                                      1.9
                                      BW
                                  Body weight
                                     (kg)
                                    Adults
                                      80
                                       
                                       
                         Children 6 < 11 years old
                                      32
[a] Transfer coefficient point estimates from a composite distribution assuming equal proportion of time spent conducting various activities.  See "Transfer Coefficient" section below.  Children 6 < 11 years old TC derived using surface area adjustment (see Section 2.3).
[b] Activity time point estimates from a composite distribution assuming equal proportion of each respective activity.  Time for children 6 < 11 years old derived using hrs/day ratio adjustment.  


Appendix B.  Summary of Occupational and Residential Non-cancer Algorithms

Average Daily Dose
Potential daily exposures for occupational handlers are calculated using the following formulas:
E=UE * AR * A * 0.001 mg/ug
where:
E = exposure  (mg ai/day),
UE = unit exposure (ug ai/lb ai),
AR = maximum application rate according to proposed label (lb ai A or lb ai/gal), and
A = area treated or amount handled (e.g., A/day, gal/day).
 
The daily doses are calculated using the following formula:
ADD=  E * AFBW
where:
ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),
E = exposure  (mg ai/day),
AF = absorption factor (dermal and/or inhalation), and
BW = body weight (kg).

Margin of Exposure
Non-cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern.  The daily dermal and inhalation dose received by occupational handlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational handlers for each exposure route.  All MOE values are calculated using the following formula:
MOE= PODADD
where:
MOE = margin of exposure: value used by HED to represent risk estimates (unitless),
POD =	point of departure (mg/kg/day), and
ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).
Appendix C.  Summaries of Dislodgeable Foliar Residue Studies and Proposed Use in Assessment

Proposed Uses for Bifenazate
                                   Commodity
                                Foliage Type[a]
                                 Product Name
                             Application Equipment
                               Application Rate
                                   (lb ai/A)
                          Maximum Number Applications
                                  Per Season
                 Herbs subgroup 19 A (except chives, chervil)
                                    Unknown
                               Florimite(R) 50WP 
                          Groundboom, Aerial Airblast
                                      0.5
                                       1
                         Fruiting vegetable group 8-10
                                    smooth
                                       
                                       
                                       
                                       
Pome fruit group 11-10
                                    smooth
                                       
                                       
                                       
                                       
                              Timothy forage hay
                                    varied
                                       
                                   Airblast
                                     0.75
                                       1
a. Based on information in the ARTF/ORETF DFR Guidance


DFR Studies Available:

Florimite(R) 50WP on Spathiphyllum: Dislodgeable Foliar Residue Study (MRID 448597-01).
(HED Review:  Memo, L. Venkateshwara, -Nov-2012, D        )

      This study was designed to collect data to evaluate dislodgeable foliar residue (DFR) dissipation for the compound bifenazate from Spathiphyllum (Peace Lily) foliage grown in a greenhouse at one site in Florida.  One field trial was conducted in two greenhouses, one containing treated  Spathiphyllum (Peace Lily) plants and the other containing untreated plants.  Primary review of the study was conducted by Versar  Inc., 7 July 2000 (MRID 448597-01).  The secondary review was conducted by HED on November __, 2012 (D________). 

      Florimite(R) 50WP is a wettable powder packaged in water soluble bags which contains 50 % bifenazate as the active ingredient.  Floramite(R) 50WP  was applied with a hand-held boom sprayer at 0.29 lb ai/A.  Three applications were made with a 30 day application interval.  DFR samples were collected were up to 28 days after the first two treatments and up to 35 days after the last treatment.  Samples were analyzed for combined residues of bifenazate and a breakdown product UCC-D3598.
      
      Study results indicate that the range of DFR values quantified were quite similar after all three applications.  The maximum DFR analyzed was 72 μg/sample (after correction for 68 percent field recovery), found on DAT-1 after the first application.  DFR values did not decline to <LOQ (i.e. 2 μg/sample) within the 21-day sampling period following the first two applications.  DFR values did decline to <LOQ by DAT-35 after the third application.
      
      Assuming first order kinetics, HED modeled dissipation rates and estimated half lives for bifenazate of 9.9 days in Florida (R[2] = 0.8433).  
      

Summary of DFR Values and Regression Analysis Results for Treated Spathiphyllum (Peace Lily) in Greenhouses with Bifenazate (MRID# 448597-01).
                                Input/Parameter
                                 Site: Florida
                                  Bifenazate
Application Rate (lb ai/A)[a] 
Study Target Rate = 0.29 lb ai/A
0.29 lb ai/A
Spray Volume (GPA) 
5 gallons/1000 ft[2]
Measured Average Day 0 Residue (ug/cm[2])
0.151
Predicted Day 0 Residue (ug/cm[2]) [b]
0.161
Slope
-0.07
Half-life (days)
9.9
R[2]
0.8433
a. The application was conducted using hand-held boom sprayer .
b. Regressions are based on data collected after second application.


Proposed use of DFR data:

   * Use the greenhouse Spathiphyllum (Peace Lily) DFR data to estimate post-application exposure for herbs subgroup 19 A (except chives, chervil), fruiting vegetable group 8-10, pome fruit group 11-10, Timothy forage hay (use predicted values).

                                     Crop
                                   DFR Data
                                     Sites
                           Proposed use of DFR Data
                               Characterization
Herbs subgroup 19 A (except chives, chervil), Fruiting vegetable group 8-10, Pome fruit group 11-10, Timothy forage hay 
                   Spathiphyllum (Peace Lily)  (Greenhouse)
                                      FL
                                   Predicted
                                  DFR values
* DFR data collected in greenhouse; is a conservative estimate.
* The formulation in the study is a wettable powder packaged in a water soluble bag whereas in one of the proposed labels (EPA Reg#400-514) the formulation is a suspension concentrate (liquid).  The second label (EPA Reg#400-503) the formulation is a wettable powder in a water soluble bag.
* The application rate was lower in the study (0.29 lb ai/A) compared to the proposed label (0.5 lb ai/A and 0.75 lb ai/A).
* Application method is not application method for proposed crops.


                                       
