UNITED STATES ENVIRONMENTAL PROTECTION AGENCY



### Date: Subject: WASHINGTON, D.C. 20460



### April 03, 2014 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### Zoxamide. Occupational and Residential Exposure and Risk Assessment for the Proposed New Use on Bulb Onions (Crop Subgroup 3-07 A).
PC Code: 10 1702 Registration No.: 10163-6414 Petition No.: 3F8164 DP Barcode: 0416'655 Decision No.: 476622 Regulatory Action: Section 3 Case No.: NA Risk Assessment Type: Occupational Exposure Assessment TXRNo.:NA CAS No.: 156052-68-5 MRIDNo.: NA 

### From:

Through: Nancy J. 

### Tsaur, Chemist**~0.567** 

### Risk Assessment Branch 3 (RAB3) Health Effects Division (7509P) Barry O'Keefe, Senior Biologist, ORE Team Leader 

# 8, rJ

# ~ Risk Assessment Branch 3 (RAB3) Health Effects Division (7509P) and

Jennifer Tyler, Chemist.... " 

### .h 

## 4 C**ltj~** Lata Venkateshwara,**En r.:** **·ronm~l J?9~t** **ion** 

### Specialist Exposure Science Advis ry 

### Co ittee**(~poSAC)** 

### Health Effects Division (7509P) To: Marcel Howard Fungicide Branch (IRB) Division (7505P)

Page 1 of 13Introduction The Registration Division (RD) requested that the Health Effects Division (HED) conduct an occupational exposure and risk assessment for the proposed new use ofthe fungicide, zoxamide, on bulb vegetables (crop group 3-07). It is HED policy to use the best available data to assess exposure. Several sources of generic data were used in this assessment as surrogate data in the absence of chemical-specific data, including Pesticide Handlers Exposure Database Version 1. 1 (PHED 1.1) and the Agricultural Handler Exposure Task Force (AHETF) database. Some ofthe se data are proprietar y, and subject to the data protection provisions ofthe Federal Insecticide, Fungicide, and Roden ticide Act (FIFRA). Note: This memorandum was reviewed by the Exposure Science Advi sory Committee (ExpoSAC) on April3, 2014.

Page 2 of 13Table of Contents 

### 1.0 Executive Summary

......... . ... . ............. . ................. . ............. . ................................. . ............... 4 2.0 Risk Assessment Conclusions and Recommendations

........................................................ 5 2. 1 Summary ofRisk Estimates

............................................................................................. 5 2.2 Data Deficiencies and Requirements
............................................................................... 6 3.0 Hazard Characterization

....................................................................................................... 6 4.0 Use Profile

........................................................................................................................... 8 5.0 Residential Exposure and Risk Estimates

............................................................................ 8 5.1 Spray Drift

...... . .. :........... . .................................................................................................. 8 5.2 Residential Bystander Post

-Application Inhalation Exposure

......................................... 9 6.0 Occupational Exposure and Risk Estimates

........................................................................ 9 6

. 1 Agricultural Occupational Handler Exposure/Risk Estimates

......................................... 9 6.3 Occupational Post

-Application Exposure/Risk Estimates

............................................. 11 6.4 Restricted Entry Interval

................................................................................................ 12 Appendix A. 

### Summary of Occupational Handler Non

-Cancer Algorithms

................................ 13

Page 3 of 13

### 1.0 Executive Summary Zoxamide is a benzamide-class fungicide used to control o omycete diseases (e.g. late blight and downy mildew). Its pesticidal mode of action is through preventing nuclear division by binding the P-subunit of tubulin and disrupting microtubulin polymerization. There are no mammalian molecular data to specifically show this mode of action in test animals

. Gowan has submitted a proposal for a new use on bulb onions. The product, Gavel ® DF75 Fungicide (EPA Reg. No. 10163-6414), is a water dispersible granule (WG) formulation containing 8.3% active ingredient (ai) by weight. Gavel® DF75 Fungicide is a mixed active ingredient (MAl) product which also contains 66.7% mancozeb by weight; this document only addresses the human health effects of zoxamide. Since zoxamide is not proposed or registered for residential use, this document only details the occupational assessment of the proposed product. Proposed Use Profile The proposed agricultural use is for broadcast foliar treatment to bulb vegetables (crop group 3- 07). The proposed maximum single application rate for this use is 0

. 17 lb ai/acre. Exposure Profile Based on the proposed use, occupational exposures to zoxamide are expected for short- and intermediate-term durations when conducting handling and post-application activities. The dermal route of exposure is not assessed because there is no systemic hazard resulting from dermal exposure. Hazard Characterization In the vast majority of studies, zoxamide did not cause any toxicity up to the limit dose. The toxicity data of zoxamide indicate that the primary target organ is the liver. Furthermore, liver and thyroid weights increased along with liver histopathological change and increases in alkaline phosphatase. A dermal point of departure (POD) is not chosen because systemic toxicity was not seen in 28-day dermal toxicity in rats up to the limit dose (1 ,000 mglkg/day). The short- and intermediate

-term inhalation PODs are based on the results of a chronic oral toxicity study in dogs. Zoxamide is not acutely toxic; it is classified as Toxicity Category III or IV for all routes of exposure (dermal, oral , and inhalation). There are no genotoxicity, mutagenicity, neurotoxicity, or immunotoxicity concerns. Nor are there developmental or reproductive toxicity concerns. Zoxamide is classified as "Not Likely to be Carcinogenic to Humans" based on the absence of increased tumor incidence in acceptable /guideline carcinogenicity studies in rats and mice. Combining Exposures/Risk Estimates The dermal route of exposure does not need to be combined with another route of exposure or included in the aggregate risk assessment because there is no identified systemic dermal hazard. Summary of Residential Exposure and Risk Es timates There are currently no registered or proposed residential uses for zoxamide.

Page 4 of 13Summary of Occupational Handler Exposure and Risk Estimates The results of the occupational handler exposure and risk assessment indicate that short- and intermediate-term inhalation risks are not ofconcern at baseline mitigation without personal protective equipment (PPE). Short- and intermediate-term margins ofexposure (MOEs) range from 7,400 to 970 , 000. Note that only engineering control (enclosed cockpit) data are available to assess risks to handlers operating aircrafts. Summary of Occupational Post-Application Exposure and Risk Estimates An occupational post

- application dermal exposure and risk assessment was not conducted because a systemic dermal hazard was not identified for zoxamide. Based on the Agency's current practices , a quantitative non-cancer occupational post-application inhalation exposure assessment was not performed for zoxamide at this time

. Ifnew policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inhalation exposure assessment for zoxamide. Restricted Entry Interval (REI) The 48-hour REI listed on the label is adequate to protect agricultural workers from post

application exposures to zoxamide.
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 Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1) and the Agricultural Handler Exposure Task Force, 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 1 • 

### 2.0 Risk Assessment Conclusions and Recommendations There are no occupational/residential risk estimates of concern associated with the proposed new uses of zoxamide on bulb onions. 

### 2.1 Summary of Risk Estimates Occupational Exposure and Risk Estimates The results of the occupational handler exposure and risk assessment indicate that short- and intermediate-term inhalation risks do not exceed HED ' s level ofconcern (i.e. the LOC is an MOE < 100) at baseline mitigation (no PPE). Since the short- and intermediate-term PODs are the same, the inhalation MOEs are also the same, ranging from 7,400 to 970,000. Dermal handler and post-application exposure and risk assessments were not conducted because a dermal hazard was not identified for zoxamide

.

1 http: //www.epa.gov/pesticides / science /handler-exposure-data.html and http: //www.epa.gov /pesticides/science /post-app-exposure-data.html Page 5 of 132.2 

### Data Deficiencies and Requirements There are no data deficiencies or data requirements for the proposed new use of zoxamide. 

### 3.0 Hazard Characterization The risk assessment for zoxamide is based on a well-characterized and complete toxicology database. Zoxamide did not cause any toxicity up to the limit dose in the vast majority of the studies. However, the chronic and subchronic dog studies indicated that the primary target organ for oral exposure to zoxamide is the liver. Additionally, liver and thyroid weights were increased along with liver hi stopathological changes and increases in alkaline phosphatase in the chronic study. Zoxamide was not observed to cause developmental/reproductive toxicity, carcinogenicity, or neurotoxicity.
A dermal POD was not chosen because systemic toxicity was not seen in a 28-day dermal toxicity study in rats up to the limit dose (1,000 mg/kg/day). Furthermore, the short- and intermediate-term inhalation PODs are based on the results of an oral chronic toxicity study in dogs, in the absence of a repeated-dose study by the inhalation route
. The inhalation study was waived based on a weight of evidence decision (HASPOC memo, K. Rury, TXR0056915). The selected POD of 48 mg/kg/day from a (LOAEL of 255 mg/kg/day) is based on body weight changes, increases in liver and thyroid weights, and increases in alkaline phosphatase. Acute Toxicit v Table 3.1. Summary of Acute Toxicity Data for Zoxamide (Technical Active Ingredient) Guideline Type ofstudy MRID Results Toxicity No. Category 870.1100 Acute Oral T oxicity (Ra t) 44731805 LDso > 5000 rog/kg IV Acute Oral Toxicity (Mouse) 44731806 LDso > 5000 mg/kg IV 870 .1200 Acute Dermal Toxicity (Rat) 44731807 LDso > 2000 mg/kg III 870

. 1300 Acute Inhalation Toxicity (Rat) 44731808 LCso > 5.3 mg/L IV Corneal opacity beginning 24 hrs post dosing III 870

. 2400 Acute Eye Irritation (Rabbit) 44731809 and ending at 72 hrs post dosing. Conjunct ivitis beginning 1 hr post dosing and resolved by Day 07. 870

. 2500 Acute Dermal Irritation (Rabbit) 44731810 No irritat ion was noted IV 44731811 The chemical is a strong dermal sensitizer: All sites challenged with test material had 870

. 2600 Dermal Sensitization (Guinea Pig) 447318 12 scattered mild redness to intense redness and NA swelling; two sites had subcutaneous hemorrhaging.

Page 6 of 13T I POD U d fi Ri k A OXlCO og1ca s se or s ss essment Table 3.3. SuDUDary ofToDcological Doses and EadpoiDu for Zo:umide for Use in Oecupational Human Health Risk**Assess~~~e~~ua** RID, PAD,

Expo sure/ Point of Uncertainty/ Level of Scenario Departure FQPA Safety Concern for Study and Toxicological Effects Factors Risk Assessment D ermal Short-Term (1

- 30 days ) A toxicity endpoint was not i dentified. and Syst emic toxicity was not seen in 28-day dermal toxicity in rats at the limit dose ( 1000 Intermed iate mg/kg/ day)

. There are no concerns for developmental or reproductive toxicity or neurotoxicity.

- Terms (l-6 month s) Inhalation Short-Term Chronic Toxicity- Dog (1

- 30 d ays) NOAEL = UFA =lOX LOAEL = 255 mg/kglday and 48 UFH= lOX LOC = 100 B ased on body weight changes , increases in liver Intermediate m g/kg/day and thyroid weights, and incre ases in alkaline -Terms (1-6 pho s ph atase
. months) Cancer (oral, C lassification : "Not likely to be Carcinogenic to Humans" based on data showing lack of dermal, treatment-related increase in tumor i ncidence in the rat and mouse carcinogenicity studies. inhalation) Mutagenic concern was not reported in the mutagenicity studies. a Pomt of Departure (POD) = A data pomt or an estimated pomt that IS denved from observed dose-response data and used to

mark the beginning ofextrapol a t ion to determine risk associated with lower environmentally relevant human exposures. NOAEL =no observed adverse effect level. LOAEL = l owest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation f rom animal to human (interspecie s). U F

H= potential variation in sensitivity among members ofthe human population (intraspecies). LOC = level ofconcern. Absor ption A dermal absorption factor is not used in thi s ass es sment because a dermal toxicity POD i s not identified b ased on a 28-day dermal toxicity study in rats. Since the short- and intermediate-term inhalation PODs are based on an oral toxicity study , inhalation absorption i s assumed to be equivalent to oral absorption ; thus, an inhalation absorption factor is not nece ssary. Body Weight The standard body weight for the general population (80 kg) is used for all expo s ure scenarios covered in this risk assessment since the endpoints selected are not developmental and/or fetal effects.

Page 7 of 13

### 4.0 Use Profile
Table 4.1

. Summary ofProposed**DirediQDs_ibr~ U"'~~icle**  Application Fonnulation Maximum Max. No. Max. PHI/ of Seasonal Timing, Type, and [EPA Reg. No.] Application Appsper Application RTI Use Directions and Limitations Equipment Trade Name" Rate Season Rate days Bulb Vegetables (Group 3-07) Do not treat plants grown for transplanting. Do not apply to the soi l or through drip irrigation Foliar 8

. 3%WG 0.17 systems
. Use this product only in commercial (ground , aerial, [10163-6414) lb a. i/A 1.33 and farm plantings

. May be used on crops 8 7 grown for seed production

. Adjuvants may be chemigation, and Gavei®75DF O.oi 7b lb ailA used (methylated seed oils ; petroleum oil handheld) Fungicide lb ai/gal concentrates; non-ionics ; organosilicones/ organosilicates)

. Use a minimum of 10 gallons per acre for bulb vegetables.
a Ponnulat10n code: WG

- water dtsperstble granules. b Application rate based on use direction of " minimum o f 10 gallons per acre for bulb vegetables ." 

### 5

.0 Residential Exposure and Risk Estimates There are no proposed or registered residential uses at this time. This proposed occupational use will not affect aggregate human health risk calculations, or the associated regulatory decisions. 

### 5

. 1 Spray Drift Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application method employed for zoxamide. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State Lead Agencies for pest icide regulation and other parties to develop the best spray drift management practices (see the Agency's Spray Drift website for more informationf The Agency has completed its evaluation ofthe new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements in spray drift management practices to reduce off-target drift with specific products with significant risk estimates associated with drift. Although a quantitative residential post-application inhala tion exposure assessment was not performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation exposure assessment was performed for flaggers. This exposure scenario is representative ofa worse case inhalation (drift) exposure and may be considered protective of most outdoor agricultural and commercial post-application inhalation exposure scenarios.

2 Available: http: //www.epa.gov/oppOOOO I /factsheets/spraydrift.htm Page 8 ofl35.2 

### Residential Bystander Post-Application Inhalation Exposure Based on the Agency's current practices , a quantitative post-application inhalation exposure assessment was not performed for zoxamide at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure (<1.3x lo -s Pa, or 9.75x10· 8 mm Hg at 25, 35, and 45°C) and the low proposed use rate (0.17lb ail A). However, volat ilization of pesticide s may be a source ofpost-application inhalation exposure to individuals nearby pesticide applications. The Agency sought expert advice and input on is sues related to volatilization ofpesticides from its Federal Insecticide, Fungicide , and Rodenticide Act Scientific Advisory Panel (S AP) in D ecember 2009, and received the SAP ' s final report on March 2, 2010 3

. The Agency is in the process of evaluating the SAP report and may, as appropriate , develop policies and procedur es to identify the need for and, subsequently, the way to incorporate post-application inhalat ion exposure into the Agency's risk assessments. Ifnew policies or procedures are developed, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for zoxamide. 

### 6.0 Occupational Exposure and Risk Estimates 6.1 Agricultural 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 distinctjob functions or tasks related to applications and exposure s can vary depending on the specifics of each task. Job requirements (amount ofchemical used in each application) , the kind s of equipment used , the target being treated, and the level of protection used by a handler can cause exposure level s to differ in a manner specific to each application event. Based on the anticipated use pa tterns and current labeling , types of equipment and techniques that can potentially be used , occupational handler exposure is expected from the proposed agricultural uses . The quantitative exposure /risk assessment developed for occupational handlers is based on several scenarios which include mixing/loading/applying the dry flowable formulati on of zoxamide. The use sites are summarized in Section 4.0. Methods of application include aerial, chemigation, groundboom, and handheld equipment. Furthermore, human flagging is prohibited on the label. Flagging to support aerial application is limited to use of the Global Positioning System (GPS ) or mechanical flaggers. Refer to Table 6.1 for a detailed list of each scenario. Occupational Handler Exposure Data and Assumptions A series of assumptions and exposure f actors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis. Application Rate: Refer to the proposed use pattern table in Section 4.0.
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,

3 Available: http: //www.epa.gov / scipoly/ SAP /meetings/2009/ 120 I09meeting.hnnl Page 9 of 13include PHED 1.1, the AHETF database, or other registrant-submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subj ect to the data protection provisions ofFIFRA. 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 Table4 ", 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 website5

. Area Treated orAmount Handled: The area treated or amount handled is based on HED ExpoSAC Policy No. 9 .1. Refer to Table 6.1 for these assumptions for each scenario. Exposure Duration: HED classifies exposures from 1 to 30 days as short-term and exposures 30 day s 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 tha t use site. For most agricultural uses, it is reasonab le to believe that occupational handlers will not apply the same chemical every day for more than a one-month time frame; however, there may be a large agribusiness and/or commercial applicators who may apply a product over a period ofweeks (e.g. completing multiple applications for multiple clients within a region). For this proposed use on onions, both short- and intermediate-term exposures are expected from occupational use. Since the PODs for short- and intermediate-term exposure are the same, the short-term assumptions and risk calculations are protective of both durations. Mitigation/Personal Protective Equipment: Results are presented for " baseline, " defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respirator. The Gavel® DF75 Fungicide product label direct mixers, loaders , applicators and other handlers to wear long-sleeved shirts, long pants, shoes plus socks, and chemical-resistant gloves made of any waterproof material. Occupational Handler Non-Cancer Exposure and Risk Estimate Equations The algoritluns use d to estima te non-cancer exposure and dose for occupational handlers can be found in Appendix A. Combining Exposures/Risk Estimates The dermal route of exposure does not need to be combined with the assessed inhalation route of exposure or included in the aggregate risk assessment because there is no identified systemic dermal hazard. Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates The results of the occupational handler exposure and risk assessment indicate that short- and intermediate-term inhalation risks do not exceed HED's LOC (i.e. an MOE< 100) at baseline mitigation (no PPE). Since the short

- and intermediate-term PODs are the same, the inhala tion MOEs are also the same, ranging 7,400 to 970,000. Note that only engineering control (enclosed

4 Available: http: //www.epa.gov/ oppOOOO 1 / science/handler-exposure-table.pdf 5 Available: http: //www .epa. gov /pesticides/science / hand ler-exposure-data.htmI Page 10 of13cockpit) data are availab le to assess ri s ks to handlers operating aircrafts. Furthermore, human flagging is prohibited on the label.
HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the engineering control (enclosed cockpits) and baseline attire (long

- sleeve shirt, long pants , shoes , and socks) ; per the Agency ' s Worker Protection Standard stipulations for engineering controls , pilots are not required to wear protective gloves for the duration ofthe application. With this level of protection , there are no risk estimates of concern for applicators.
tfable 6.1. Oc:npational Hudler Esposare and Risk Estbutes for Zcmtmicle.
Base line Area Basel ine I nh alation lnha lati on Maximum T reated or

U ni t A ppli catio n Am o unt Exposur e Scenari o Crop or T arget• Exposureb R ate• Handled Dosee MO Er Dailyd**glib** ai lb ail A Ac res m g/kg/d a y ST i lT LOC 

### = 100 Mixer/Loader Mixi ng/Load ing Dry F low abl es for Typi cal Field C ro ps 0. 1 7 3 5 0 0.0065 1 7,4 00 Aerial an d Cbem iga ti on A pp li cat ion M i xi ng/Loading Dry Flowables f or 8 .96 Groundboom Application Typical Field C rops 0. 1 7 80 0

.00149 32, 000 Applicator Appl y ing S prays f or Aerial Typical Field C ro ps 0.068 0 .1 7 35 0 0.0000 4 9 4 9 70, 000 Appl icatio n A pply ing Sprays fo r Gro undboom Typical Fi e ld C rops 0

. 34 0

. 17 80 0 .00 00 565 850, 0 00 Application Mixer/Loader/Applicator MIU A Dry F lowa bles for Typ ical F ield C ro ps 0 .0 1 7 1000 Mech anically-Pressuri zed H andgun 3.9 0.000 809 5 9 ,000 Spr ayers (Foliar) lb ai/gal g all ons
a " T y ptcal Fteld Cr ops" tn clude bulb vege tabl es (Group 3-07)

. b Based on the "Occupational Pesticide Handler U nit Expo sure Surrogate Re fere nce Table " (March 2012 ); Level of mitigation= Baseline except for aerial appli cator which includes engineering co ntrols. c Based on the maxi mum application r ates on the proposed lab els (Reg

. No

. 10 163 -641 4, Gavel® 75 DF Fungic i de)

. d E xpos ure Scienc e Advisory Council P olicy #9

. 1

. e Inhala tio

n Dose= Derm al Unit E xposure (Jlg/lb ai) x Conversion F act

or (0.001 mgf Jlg) x Ap plica tion Rate (lb ai/acre or ga l) x Area T reated or Amount Handl e d Dail y (A or gal/d ay) + BW ( 80 k g). f Inhalation MOE= Inhalation NOAEL (48 mgfkgfday) + Inhalation Dose (m gfkgf day). 

### 6.3 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 activiti es related to crop production , such as scouting for pe sts or harvesting. Post-application exposure levels vary over time and depend on s uch things as the type of activity , the nature ofthe crop or target that was treated, the type ofpestiCide application, and the chemical ' s degradation properties. In addition, the timing of pes ticide applications , relative to harvest activities , can greatly reduce the potential for post-application exposure.
Page 11 of 13An occupational post-application dermal exposure and risk assessment was not conducted because a systemic hazard was not identified for the dermal route of exposure for zoxamide. Occupational Post-Application Inhalation Exposure/Risk Estimates Based on the Agency's current practices, a quantitative post-application inhalation exposure assessment was not performed for zoxamide at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure (<1.3x 10·5 Pa, or 9.75x 10·8 mm Hg at 25, 35, and 45°C) and the low proposed use rate (0.17 lb ail A). However, there are multiple potential sources of post-application inhalation exposure to individuals performing postapplication activities in previously treated fields. These potential sources include volatilization ofpesticides and resuspension ofdusts 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 6

. The Agency is in the process of evaluating the SAP report as well as available post-application inhalation exposure data generated by the ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupa tional post-application inhalation exposure into the Agency's risk assessments. Ifnew policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post-application inhalation exposure assessment for zoxamide. 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 ofpesticides 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 scenarios. 

### 6.4 Restricted Entry Interval Zoxamide is classified as Toxicity Category III via the dermal route. It is a moderate irritant to eyes, it is not irritating to the skin, but it is a skin sensitizer. Typically , the REI specified on the proposed label is based on the acute toxicity of the active ingredient. Under 40 CFR 156.208 (c) (2) (iii) , active ingredients classified as Acute III or IV for acute dermal, eye irritation, and primary skin irrigation are assigned a minimum of 12 hours for the REI. Thus, the 48-hour REI on the proposed label is acceptable for bulb onions.

6 Available: http ://www .epa.gov / s cipoly/ SAP / meetings/2009/ 120 I09meeting.html Page 12 of 13Appendix A. Summary of Occupational Handler 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 (llg 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: E*AF ADD= BW where: ADD = average daily dose absorbed in a given scenar io (mg ailkg/day) , E = exposure (mg ai!day) , AF =absorpt ion 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 ofthe 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: 

### POD MOE = ADD 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 scenar io (mg ai/kg/day).

Page 13 of 13