Date: 

Subject: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

July 22, 20 14 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Halauxifcn-methyl. Occupational and Residential Exposure and Risk 

Assessment to Support the Registration of the New Active Ingredient on Wheat, 

Barley, and Triticale. 

PC Code: I 1750 I 

Decision No.: 470169 

Petition No.: 2E8086 

DP Barcode: 04161 29 

Registration No.: 62719-AAE, AAG. AAN. AAR, AAU 

Regulato ry Action: Section 3 Registration 

Risk Assessment Type: Exposure Assessment 

TXR No.: NA 

Case No.: A 

CAS No.: 94383 1-98-9 

MRID No.: NA 

From: 

Through: 

To: 

Introduction 

40 CFR: New Active Ingredient 

Za ida Figueroa, Industrial Hygienist 

Risk Assessment Branch II 

Health Effects Division (7509P) 

Christina Swartz, Branch Chief ~ A __, 

Risk Assessment Branch 11 J \._\ 

Health Effects Division (7509P) 

and 

Matthew 

Matthew 

Crowley

Lloyd. ExpoSAC 

, ExpoSAC 

Reviewer 

Reviewer t~ 

Exposure Science Advisory Committee ( xpoSAC) I HED 

Maggie Rudick/Kable Bo Davis. PM Team 25 

Herbicide Branch 

Registration Division (7505P) 

The Registration Division (RD) requested that the Health Effects Division (I IED) conduct an 

exposure and risk assessment for proposed uses of the new herbicide halauxifen-methyl to 

control annual broad leaf weeds in wheat, barley, and triticale. There are no residential uses 

proposed for halauxifen-methyl at this time; therefore, this risk assessment only addresses the 

potential occupational exposures associated with the proposed uses. 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: the Pesticide 

Page I of 17 
Handlers Ex posure Database Version 1.1 (PHED 1. 1 ); and the Agricultural Handler Exposure 

Task Force (AHETF) database. Some of these data are proprietary, and subject to the data 

protection provisions of the Federal Insecticide, Fungicide. and Rodenticide Act (FIFRA). 

Note: This memorandum was reviewed by the Exposure Science Advisory Committee 

(ExpoSAC) on May I. 20 14. 

Page 2of 17 
Table of Contents 

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

2.0 Risk Assessment Conclusions and Recommendations ........................................................ 6 

2.1 Summary of Risk Estimates ....................... ......... ............... .............................................. 6 

2.2 Label Recommendations from Occupational Assessment.. ............................................. 6 

2.3 Label Recommendations from Residential Assessment ................................................ .. 6 

2.4 Data Deficiencies and Requirements .................. ....................... ...................................... 6 

3.0 I lazard Characterization ....................................................................................................... 6 

4.0 Use Profile ....................................... .................................................................... ... ........... .. 8 

5.0 Residential Exposure and Risk Estimates ............... ............ ............ ......................... .......... 10 

6.0 Non-Occupational Spray Drift Exposure and Risk Estimates ........................................... 10 

7.0 Non-Occupational Bystander Post-Appli cation Inhalation Exposure and Risk Estimates 10 

8.0 Occupational Exposure and Risk Estimates ...................................................................... l 0 

8.1 Occupational Handler Exposure/Risk Estimates ................................................. ........... 10 

8.2 Occupational Post-application Exposure/Risk Estimates .............................................. 15 

8.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates ...................... 15 

8.2.2 Occupational Post-application Dermal Exposure/Risk Estimates .......................... 15 

Appendix A. Summary of Occupational and Residential Non-cancer Algorithms ..................... 17 

J>agc 3 of 17 
1.0 Executive Summary 

Halauxifen-methyl is a new arylpicolinate post-emergence herbicide with proposed uses on 

cereal grains to control a variety of annual broadleaf weeds such as common lambsquarters, 

redroot pigweed, cleavers, hen bit, wild buckwheat and mustards. The pesticidal mode of action 

is as a synthetic auxin. 

This new active ingredient (ai) is being reviewed by the Agency as part of a global joint review 

project with Canada [Pesticide Management Regulatory Agency (PMRA)] and Australia 

[Australian Pesticides and Veterinary Medicines Authority (APVMA)J. The proposed uses are 

the first uses of halauxifen-mcthyl in the United States. Halauxifen-methyl may be applied as a 

post-emergence broadcast spray through a variety of application methods including ground and 

aerial equipment at a maximum single application rate of 0.009 l lb ai/ A. 

This assessment addresses exposure and risk associated with the proposed end-use product for 

halauxifen-methyl when used as directed by occupational handlers. There is a potential for 

occupational exposure associated with handler activities (i.e., mixing, loading, and applying). 

Post-application exposure is expected for workers re-entering treated areas. Based on the 

proposed labels· use pattern/directions (e.g., 1-2 applications per season), short- term ( 1 to 30 

days) and intennediate-term (I to 6 months) are expected for handlers. Long-term exposures 

(greater than 6 months) are not anticipated. 

There arc no registered or proposed residential uses, or commercial/professional uses at 

residential sites associated with halauxifcn-methyl at this time. Therefore, a quantitative 

residential exposure assessment is not required. 

Hazard Profile and Points of Departure (POD) 

Halauxifen-methyl has low acute toxicity via the oral and dermal routes; and no dermal or eye 

irritation (Toxicity Category Ill or IV for all categories). It is not a skin sensitizer. HED has 

determined that the toxicology database for halauxifcn-methyl is complete and adequate to assess 

occupational exposure. Halauxifen-methyl and its major metabolite, XDE-729 acid, show 

significantly different toxicological profiles. For dermal exposure, external exposure is to the 

parent, but sy$temic internal exposure is expected to be to the acid. A 28-day dermal toxicity 

study on XDE-729 acid in rats did not result in systemic or dermal toxicity up to the limit dose of 

1.000 !Tig/kg/day. A dermal toxicity study was not conducted on halauxifen-methyl. An 

adjus11nent of the No Observed Adverse Effect Level (NOAEL)/Lowest Observed Adverse 

Effect Level (LOAEL) indicated that toxicity is only observed well above the limit dose tested 

(1,00P mg/kg/day). Therefore, no short- or intermediate-term dem1al endpoints of concern were 

identified. For short- and intermediate-term inhalation risk assessment, a POD of 3 mg/kg/day 

wa~ selected from a 90-day rat oral study on halauxifen-methyl to protect for an increased 

Cyplal induction aud the molecular initiating event identified for toxicity to the liver from 

halauxifon-methyl. Since the NOAEL for inhalation risk assessment was chosen from an oral 

study, it was assumed that toxicity via the inhalation route is equivalent lo oral toxicity. HED 

determined that a subchronic inhalation study is not required; therefore, an additional database 

uncertainty fac;tor (UF) is not required (HASPOC, TXR #0056954). 

Page 4or17 
The level of concern (LOC) for occupational inhalation risk assessments is a margin of exposure 

(MOE) of I 00, based on the combined interspecies ( 1 OX) and intraspecies (I OX) uncertainty 

factors. Halauxifen-methyl is considered not likely to be carcinogenic and, therefore, there is no 

cancer risk associated with the proposed uses. 

Occupational Handler Exposure 

No chemical-specific handler exposure data were submitted in support of this registration: 

therefore, HED relied on surrogate data in accordance with standard policies. Default 

assumptions established by the l IED Science Advisory Counci I for Exposure (Expo SAC) were 

used for parameters such as body weight and area treated. 

Occupational assessments for halauxifen-methyl are based on inhalation exposures only. All 

occupational handler scenarios for the proposed uses resulted in MO Es greater than the LOC of 

100 at baseline attire (i.e .. long-sleeved shirt and long pants, shoes plus socks) or engineering 

control for aerial applications (enclosed cockpits), and therefore, are not of concern. The 

proposed labels require applicators and other handlers to wear baseline attire and personal 

protective equipment (PPE; chemical-resistant gloves). No additional PPE will be needed on the 

proposed labels. Although a POD from an oral study was used to assess handler inhalation risk. 

the calculated MOEs are all ;:::2,500, thus providing an ample margin to account for any 

uncertainties in the route-to-route extrapolation. 

Occupational Post-application Exposure 

Inhalation 

Based on the Agency's c urTent practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment is not being performed for halauxifen-methyl 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 halauxifen-methyl. 

Dermal 

Occupational post-application risk estimates for agricultural workers fo llowing treatments to 

agricultural crops were not assessed. since no dermal endpoint of concern was identified. 

I lalauxifen-methyl is classified as Toxicity Category IV via the dermal route and for skin 

irritation, and Toxicity Category Ill for eye irritation potential. It is not a skin sensitizer. The 

restricted entry interval (REI) of 12 hours listed in the proposed labels is adequate to protect 

agricultural workers from post-application exposures to halauxi fen-methyl. 

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 PH ED I . I 

Page 5 of 17 
database; and the AHETF database, arc ( 1) subject to ethics review pursuant to 40 CFR 26, (2) 

have received that review, and (3) are compli ant 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 

2.1 Summa ry of Risk Estimates 

HED has identified no occupational risks of concern for the proposed uses of halauxifen-methyl 

to control annua l broad leaf weeds in wheat, barley, and triticale. 

2.2 Label Recommendations from Occupational Assessment 

None. 

2.3 Label Recommendations from Residential Assessment 

None. 

2.4 Data Deficiencies and Requirements 

None. 

3.0 Hazard Characterization 

Acute Toxicity 

Halauxifen-methyl has low acute toxicity via the oral and dermal (Category IV) routes. An acute 

inhalation study was not conducted due to problems generating a respirable test atmosphere. It is 

minimally irritating to the eye (Category III), non-irritating to the skin (Category IV), and is 

negative for skin sensitization. 

Table 3.1. Acute Toxicity of Halauxifen-methyl (XDE-729 methyl). 

Guideline No./Study Type MRID Results Toxicity 

Category 

870. 11 00 /\cute oral toxicity (rat) 48557814 LDso > 5000 mg/kg IV 

870. 1200 Acute dermal toxicity (rat) 48557816 LDso > 5000 mg/kg IV 

1 Imp ://www2. epa. gov/pest ic ide-sc icnce-an d-assess in g-pest ic ide-ri sks/ occupation a I-pesticide-handler-exposure-data 

and http ://www 2. epa. gov/pesticide-science-and-assess in g-oest ic ide-ri sks/occupat io na I-pest ic ide-post-app I icat ionexposurc 

Page 6of 17 
870.1300 Acute inhalation toxicity (rat) 48557818 Study not submit1ed based on - inability to generate lest 

atmosphere. 

870.2400 Acute eye irritation (rabbit) 48557820 Mild eye irritant Ill 

870.2500 Acute dermal irritation (rabbit) 48557822 1ot a dermal irritant IV 

870.2600 Skin sensitization (guinea pig) 48557824 Nol a dermal sensitizer NA 

Toxicological PODs Used for Risk Assessment 

The toxicology database for halauxifen-methyl is complete and adequate to assess the 

occupational exposures associated with the proposed uses. For dermal exposure, external 

exposure is to the parent, but systemic internal exposure is expected to be to the acid. A 28-day 

dermal toxicity study on XDE-729 acid in rats did not result in systemic or dermal toxicity up to 

the limit dose of 1,000 mg/kg/day. A dermal toxicity study was not conducted on halauxifenmethyl. Using oral studies on the acid with a dermal absorption factor for halauxifen-methyl 

(24%), toxicity was observed only at doses exceeding the limit dose. Therefore, no short- or 

intermediate-term dermal endpoints of concern were identified. 

A 90-day oral rat study was used to select the dose and POD of 3.0 mg/kg/day for short- and 

intermediate-term inhalation risk assessment based on increased Cyp 1 a I induction and to protect 

for the initial molecular event identified for liver toxicity from halauxifen-methyl. The NOAEL 

of 10 mg/kg/day was based on the increased Cyp I a I induction effect. The effects at the LOAEL 

of 53 mg/kg/day were based on liver enlargement and histopathology. The selected POD of 3.0 

mg/kg/day is considered conservative and a protective endpoint for potential effects from 

inhalation or oral (swallowing of non-respirable particles) absorption. Furthermore, HED 

determined that a subchronic inhalation study is not required; therefore. an additional database 

uncertainty factor (UF) is not required (HASPOC, TXR #0056954). 

There are no other uncertainty factors needed to account for missing data. Therefore, the LOC 

for occupational inhalation risk assessments is a MOE of I 00, based on the combined 

interspecies ( 1 OX) and intraspecies (1 OX) uncertainty factors. 

Halauxifen-methyl is considered not likely to be carcinogenic: therefore, there is no cancer risk 

associated with the proposed uses. 

A summary of the toxicological doses and endpoints for halauxifen-methyl is provided in Table 

3.2. 

Page 7of17 
Table 3.2. Summary of Toxicological Doses and Endpoints for Halauxifen-methyl for Use in Occupational Human 

Health Risk Assessments. 

Exposure/ Point of Uncertainty Level of Concer n 

fo r Risk Study and Toxicological Effects Scenario Departure Factors Assessment 

Dermal ShortTerm ( 1-30 

days) and No ha1ard from dermal exposure was idcn1ificd in the available da1abasc: therefore. no risk is expected 

ln1crmcdia1e- from this exposure scenario. 

Term ( 1-6 

months) 

90-day oral toxicity in the ra1 (halauxifenPOD = 3.0 me1hyl). 

Inhalation mg/kg/day Increased hepatic Cyp la I expression 

Shon-Tenn (\- (molecular initiating event for toxicity from 

30 days) and UFA= I Ox Occupational LOC /\hR activation) \\as observed at 10 

Intermediate- (Inhalation UF11=10x fo r MOE= 100 mg/kg/day. 

term ( 1-6 toxicity 

considered [Note: Study NOA EL= I 0 mg/kg/day months) equivalent to increased Cyp I a I induction elTect. LOA EL 

oral toxicity.) based on liver enlargement and pathology at 

53 ml!fkg/day.] 

Cancer (oral. Classification: Not likely to be carcinogenic to humans at dose levels that do not induce Cyp I a I 

expression. The cRfD is considered protective of potential cancer effects in the absence of long-term dermal. toxicity data on halauxifcn-rncthyl because it protects for the molecular ini1ia1 ing event for liver toxicity inhalation) from AhR activation. 

Point of Depanure (POD) = /\ data point or an estimated poinl that is derived from ob erved dose-response data and used to 

mark the beginning of extrapolation 10 determine risk associated with lower environmentally relevanl human exposures. OAEL 

= no observed adverse effect level. LO/\EL = lowesl observed adverse elTecl lt.:vel. UF = uncertainty factor. UFA= 

extrapolation from animal to human {interspecies). UF11 = potential variation in sensitivity among members of the human 

population (intraspecics). MOE= margin of exposure. LOC - level of concern. eRfD = chronic reference dose. 

Absorption: 

No inhalation absorption data are available; therefore, toxicity by the inhalation route is 

considered to be equivalent to the estimated toxicity by the oral route of exposure. 

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. 

4.0 Use Profile 

Halauxifen-methyl products are intended to be used as post-emergent herbicides for the control 

of annual broad leaf weeds such as common lambsquarters. red root pigweed. cleavers. henbit, 

wild buckwheat and mustards in wheat, barley, and triti cale. A summary of the use directions is 

provided in Table 4.1. 

Four agricultural products are proposed for use on wheat, barley, and triticale: Gf-2685, GF2686, GF-2687, and GF-2688. These end use products may be applied through a variety of 

application methods including: aerial and ground equipment. These products are not to be 

applied using any type of chemigation equipment. 

Page 8 of 17 
GF-2685 (EPA Reg. No. 6271 9-AAN) is formulated as a water dispersible granule (WG) which 

contains 10.4% of the active ingredient halauxi fen-methyl. GF-2685 is generally applied 2 times 

per growing season at the lower single application rate of 0.0045 lb ai/A. The recommended 

max imum single appli cation rate is 0.0091 lb ai/A. 

GF-2686 (EPA Reg. No. 62719-AAR) is formulated as a water dispersible granule and contains 

two active ingredients (ai): halauxifen-methyl (I 0.4% ai) and florasulan1(I0% ai). GF-2686 is 

generally applied 1 time per growing season at the maximum single application rate of 0.0049 lb 

ai/A. 

GF-2687 (EPA Reg. No. 62719-AAE) is formulated as a water dispersible granule and contains 

two acti ve ingredients: halauxifen-methyl (20.94% ai) and florasulam (20% ai). GF-2687 is 

generally applied 1 time per growing season at the maximum single application rate of 0.0049 lb 

ai/A. 

GF-2688 (EPA Reg. No. 6271 9-AAG) is formulated as an emulsifiable concentrate (EC) and 

contains two active ingredients: halauxifen-methyl (1 .6% ai) and fluroxypyr (34.9% ai). GF2688 is generally applied 1 time per growing season at the maximum single application rate of 

0.0058 lb ai/ A. 

Based on the use patterns (i.e., 1-2 applications per season) and resistance management practices, 

the duration of exposure for the proposed uses is expected to be short-term (1 to 30 days) and 

intermediate-term ( 1 to 6 months). Long-term exposures (greater than 6 months) are not 

anticipated. 

The PPE statement on the proposed labe ls requires applicators and other handlers to wear: longsleeved shirt and long pants, shoes plus socks and chemical-resistant gloves. 

Table 4.1. Summary of se Directions for the Proposed scs of Halauxifen-mcthyl. 

Product Method of Application Max. ll.ate No. Appl. Add itiona l Crop % A.I. Application Formu lation Equipment• Rates per season per seasont Information 

0.009 1 lb 1-2 

GF-2685 WG I 0.4% XDE-729 ai/A 0.0091 lb ail A (depending 

on rate) Do not apply this 

10.4% XDE-729: 0.0049 lb 1-2 product via 

GF-2686 WG I 0% Florasulam ai/A 0.0049 lb ai/A (depending chemigation systems. 

on rate) PHI = 60 days: REI = 13arley. PosH:rm:rgent: 1-2 12-hour Triticalc. GF-2687 WG 20.9% XDE-729: A.:rial or 0.0049 lb 0.0049 lb ai/A (depending Wheal 20% Florasulam Ground boom ai/A on rate) 

Do not apply this 

1.6°0 XDE-729: 0.0058 lb 1-2 product via 

GF-2688 EC 34.9% ai/A 0.0058 lb ai/A (depending chcmigation systems. 

Fluroxypyr on rate) PHI - 60 days: REI = 

24-hour 

·j· The minimum proposed spray volume 1s 3 gal/A for aerial apphca11011 s and 8 gal/A for ground apphcat1011s. 

~ Do not apply halauxifcn-methyl more than two growing seasons per year (i.e., Spring and/or Fall). 

Page 9of 17 
5.0 Residential Exposure and Risk Estimates 

There are no registered or proposed residential uses and/or commercial uses at residential sites of 

hal auxifen-methyl at this time. Therefore, a residential exposure assessment is not required. 

6.0 Non-Occupational Spray Drift Exposure and Risk Estimates 

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) employed 

for halauxifen-methyl. 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 Stale 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 has also developed a policy on how to 

appropriately consider spray drift as a potential source of exposure in risk assessments for 

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. The approach is outlined in the revised (20 12) Standard Operating Procedures for 

Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Ori ft. This document outlines the quantification 

of indirect non-occupational exposure to drift. 

7.0 Non-Occupational Bystander Post-Application Inhalation Exposure and Risk 

Estimates 

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 volatili zation 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, 20 I 0 (http:l/vvww.regulations.gov/#!documentOetail;D=EPA-HQ-OPP-2009-0687-

0037). The agency has eva luated the SAP report and has developed a Volatilization Screening 

Tool and a subsequent Volatilization Screening Analysis 

(http://www.regul ations.gov/# !docketDetail;D=EPA-HQ-OPP-20 14-02 19). 

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 

halauxifen-methyl. 

8.0 Occupational Exposure and Risk Estimates 

8.1 Occupational Handler Exposure/Risk Estimates 

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

application process. H ED 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 

Page 10of 17 
treated, and the level of protection used by a handler can cause exposure levels to di ff er in a 

manner specific to each application event. 

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

techniques 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: 

Mixing/Loading Liquids for Aerial Application. 

Mixing/Loading Liquids for Groundboom Application, 

Applying Sprays with Aerial Equipment, 

Applying Sprays with Groundboom Equipment. and 

Flagging to support Aerial 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: The maximum single application rates listed on proposed labels were used to 

assess handler exposure scenarios (see 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, 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 Table2

" , 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 website3

. 

Area Treated: The inputs for area treated were based on information in ExpoSAC Policy 9.1 and 

include: 

1,200 acres for aerial applications to high acreage crops, 

350 acres for flaggers to support aerial applications to high acreage crops, and 

200 acres for groundboom applications to high acreage crops. 

Exposure Duration: HED classifies exposures from I 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 

2 Available: http://www2.epa.gov/sites/production/filcs/2015-09/documents/handler-cxposurc-table-2015.pdf 

3 Available: http://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/occuP.ational-pesticide-handlerexposure-data 

Pagellofl7 
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 large agribusinesses and/or 

commerc ia l applicators who apply a product over a period of weeks (e.g., completing multiple 

applications for multiple clients within a region). 

No data on the number of exposure days per year was provided. Based on the proposed labels' 

use panern/directions (e.g., 1-2 applications per season), short- term (I to 30 days) and 

intermediate-term (l to 6 months) are expected for handlers. Long-term exposures (greater than 

6 months) are not anticipated. 

Mitigation/Personal Protective Equipment: Estimates of dermal and inhalation exposure were 

calculated for various levels of PPE. Results are presented for .. baseline,'' defined as a single 

layer of clothing consisting of a long sleeved shi11, long pants, shoes plus socks, no protective 

gloves, and no respirator. as well as baseline with various levels of PPE as necessary (e.g .. 

gloves, respirator, etc). The halauxifen-methyl product labels direct mixers, loaders, applicators 

and other handlers to wear: long-sleeved shirt and long pants, shoes plus socks, and chemicalresistant gloves. 

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations 

The algorithms used to estimate non-cancer exposures and doses for occupational handlers can 

be found in Appendix A. 

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates 

Table 8.1 presents the estimated short- and intermediate-term inhalation risk estimates for 

occupational handlers. All occupational handler scenarios for the proposed uses resulted in 

inhalation risk estimates that are greater than the LOC of I 00 (i.e., not of concern) at some level 

of risk mitigation (i.e., baseline attire with no respirator; engineering control for aeri al 

applications - enclosed cockpits). The lowest inhalation MOE identified for handlers conducting 

mixer/loader activities with WDG for aerial applications was 2,500. No additional PPE 

recommendations are needed on the proposed labels. 

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 ational 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 naggers for aerial pesticide 

applications has decreased steadily from ~ 15% in the late l 990's to only I% in the most recent 

(20 12) NAAA survey. The Agency will continue to monitor all available infonnation sources to 

best assess and characterize the exposure potential for human flaggers in agricultura l aerial 

applications. 

HED has no data to assess exposures to pilots using open cockpits. The onl y data available are 

for exposures of pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

Page 12 of 17 
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. 

Page 13 of 17 
Table 8. 1. Short- a nd Intermed iate-Term Occupational Hand ler Exposure and Risk Estimates for ll alauxifen-mcthyl. 

Exposure Scena rio Mitigation Inhalation Unit Application Rate' Arca Treatedd Inhalation 

Level• Exposure b Dose• 

(μglib ai) (mg/kg/day) 

1 ixer/Loader 

Mixing/Loading WDG for Baseline 8.96 0.009 1 lb ai/ A 1.200 A 0.00 1220 

Aerial 

0.00..19 lb ai/A 0.000659 

Mixing/Loading WDG for Basdine 8.96 0.009 1 lb ai//\ 200 A 0.00020..t 

Groundboom 

0.00..19 lb ai//\ 0.000 11 0 

Mixing/l.oading Liquids Baseline 0.219 0.0058 lb ai/A 1.200 A 0.0000 19 

for Aerial 

Mixing/Loading Liquids Baseline 0.219 0.0058 lb ai/A 200A 0.000003 18 

for Grounclboom 

Applicator 

Applying Sprays for Engineering 0.00-19 0.009 1 lb ai/A 1.200 A 0.00000067 

Aerial Application control 

(enclosed 0.0049 lb ai/A 0.00000036 

cockpits) 0.0058 lb ail/\ 0.000000..t3 

Applying Sprays for Baseline 0.34 0.009 1 lb ai/A 200 /\ 0.00000774 

Grounclboom Application 

0.00..!9 lb ail/\ 0.00000..t 16 

0.0058 lb ai/A 0.00000493 

Flaggcr 

Applying Sprays for Baseline 0.35 0.009 1 lb ai/A 350 /\ 0.0000 139 

Aerial Application 

0.00..19 lb ai/A 0.0000075 

0.0058 lb ai/A 0.00000889 .. a. M111ga11on level: baseline (long-sleeved shirt and long panl . shoes plus socks) or c11g111ccnng control (cnckiscd cockpits) lor acrrnl 

applications. 

b. Unit Exposures based on Al IETF/PHED. 

c. Application Rates based on proposed use on labels. 

d. Exposure Science Advisory Council Policy No. 9.1. 

c. Inhalation Dose (mg/kg/day) - Daily Unit e xposure (11g/lb ai) x Application Rate (lb ai/acrc) x Arca Treated I Body Weight (80 kg). 

f. Inhalation ,.,!OE I IED (3.0 mg/kg/day)/ Inhalation Daily Dose (mg/kg/day). LOC I 00. 

Page 14 of 17 

Inhalation 

~IOE' 

2.500 

..t.600 

15.000 

27.000 

160.000 

9..t0.000 

..t.500.000 

8.300.000 

7.000.000 

390.000 

720.000 

6 10.000 

220.000 

400.000 

3..t0.000 
8.2 Occupational Post-application Exposure/Risk Estimates 

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

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

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

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity. the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical 's degradation properties. [n addition, the timing of pesticide applications, 

relative to harvest activities. can greatly reduce the potential for post-application exposure. 

8.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates 

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

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

include volatilization of pesticides and 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, 20 I 0 

(http://www.regulations.gov/# ! documentOetail;D=EP A-HQ-0 PP-2009-068 7-003 7). 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 halauxifen-methyl. 

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

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

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

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

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenari os. 

8.2.2 Occupational Post-application Dermal Exposure/Risk Estimates 

Quantitative occupational post-application risk estimates for agricultural workers following 

treatments to agricultural crops were not assessed, since no dermal endpoint was identified. 

Dislodgeable Foliar Residue (DFR): In accordance with 40CFR 158, DFR data are required for 

all occupational (e.g., crop, nursery, greenhouse use sites) uses that could result in postapplication exposure to foliage. In the absence of chemical-specific DFR data, EPA uses default 

Page 15of17 
values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a 

revised default values for the fraction of the application rate available for transfer after a foliar 

application (FAR). These values are based on an analysis of 19 DFR studies. Since that time, the 

Agricultural Re-entry Task Force has submitted information (MRID 49299201) that corrects an 

application rate eITor made in the original submission of "ARF039 - Determination of Dermal 

and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse" 

(EPA MRID 4534450 I). As a result, the range of F AR values was revised from 2% - 89% to 2% 

- 47%. Jn the 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 DFR data for a single chemical. At this time, the ARTF submission did not alter the 

selection of 25% as the reasonable, high-end default value. Because DFR data are not available 

for halauxifen-methyl, EPA is using the default value of 25%. Although there may be a small 

degree of uncertainty in the use of the default DFR value for halauxifen-methyl (i.e., there is a 

small chance that the F AR value may exceed the applicable default val ue), it is likely that the 

health-protective aspects of EPA's occupational post-application assessment methodology will 

more than compensate for this potential uncertainty. For example, when assessing residential 

and occupational post-application exposure to gardens and ornamentals, EPA assumes the 

fo llowing: 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, etc); individuals perform the same post-application activities performed in the 

transfer coefficient study day after day (e.g., weeding, harvesting, pruning, etc.); and individuals 

engage in these post-application activities for a high-end amount of time every day (represented 

by data reflecting time spent gardening based on survey data). 

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. Since no dermal endpoint of concern was identified for 

risk assessment, a DFR study is not requested for halauxifen-methyl at this time. In this 

instance, it is unlikely that DFR data would be needed to further re fine exposure assessments or 

would add appreciably to our overall understanding of the availability of dislodgeable foliar 

pesticide residues for halauxifen-methyl. This decision of not requesting a DFR study might 

need to be reconsidered if there is a change in use patterns or toxicological endpoints for 

halauxi fen-methyl. 

Restricted Entry Interval (REI) 

Halauxifen-methyl is classified as Toxicity Category IV via the dermal route and for skin 

irritation and Toxicity Category Ill for eye irritation potential. It is not a skin sensitizer. Under 

40 CFR 156.208 (c) (2) (iii), ai's classified as Acute III or IV for acute dermal, eye irritation and 

primary skin irritation are assigned a I 2-hour REI. Therefore, the [I 56 subpart Kl Worker 

Protection Statement interim REI of 12 hours is adequate to protect agricultural workers from 

post-application exposures to halauxifon-methyl. This is the REI listed on the proposed labe ls, 

and is considered protective of post-application exposure. 

Page l6 of l7 
Appendix A. Summary of Occupational and Residential Non-cancer Algorithms 

Occupational Non-cancer Handler Algorithms 

Potential daily exposures for occupational handlers are calculated using the following formulas: 

where: 

E 

UE 

AR 

A 

= 

= 

E=UE *AR *A * 0.001 mg/ug 

exposure (mg ai/day), 

unit exposure (μg ai/lb ai), 

maximum application rate according to proposed labels (lb ai/A), and 

area treated (e.g .. A/day). 

The daily doses are calculated using the fo llowing formula: 

where: 

ADD 

E = 

AF 

BW = 

ADD= E*AF 

BW 

average dail y dose absorbed in a given scenario (mg ai/kg/day), 

exposure (mg a i/day), 

absorption fac tor (inhalation). and 

body weight (kg). 

Margin of Exposure: Non-cancer risk estimates for each application handler scenari o are 

calcul ated using a MOE, which is a ratio of the toxicological endpoint to the daily dose of 

concern. The daily inhalation dose received by occupational handlers is compared lo 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: 

·where: 

MOE = 

POD = 

ADD 

POD 

MOE= -

ADD 

margin of exposure: value used by I JED to represent risk estimates (unitlcss). 

point of departure (mg/kg/day), and 

average daily dose absorbed in a given scenario (mg ai/kg/day). 

Page 17of 17