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 

Risk Assessment Type: Occupational Exposure Assessment Case No.: NA 

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 

Risk Assessment 

O'Keefe, Senio

Branch 

r Biologist, 

3 (RAB3) 

ORE Team Leader 8, rJ ~ 

Health Effects Division (7509P) 

and 

Jennifer Tyler, Chemist.... " .h 4C ltj~ Lata Venkateshwara, Enr.:·ronm~l J?9~tion Specialist 

Exposure Science Advis ry Co ittee (~poSAC) 

Health Effects Division (7509P) 

To: Marcel Howard 

Fungicide Branch (IRB) 

Division (7505P) 

Page 1 of 13 
Introduction 

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

occupational exposure and risk assessment for the proposed new use of the 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 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 April3, 2014. 

Page 2 of 13 
Table of Contents 

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

2.0 Risk Assessment Conclusions and Recommendations ........................................................ 5 

2.1 Summary of Risk 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 oomycete 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 Estimates 

There are currently no registered or proposed residential uses for zoxamide. 

Page 4 of 13 
Summary 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 of concern at baseline mitigation without personal 

protective equipment (PPE). Short- and intermediate-term margins of exposure (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. 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 zoxamide. 

Restricted Entry Interval (REI) 

The 48-hour REI listed on the label is adequate to protect agricultural workers from postapplication 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 website1

• 

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 of concern (i.e. the LOC is an 

MOE < 1 00) 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 13 
2.2 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 histopathological 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 Toxicitv 

Table 3.1. Summary of Acute Toxicity Data for Zoxamide (Technical Active Ingredient) 

Guideline Type of study MRID Results Toxicity 

No. Category 

870.1100 Acute Oral Toxicity (Rat) 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. 

Conjunctivitis beginning 1 hr post dosing 

and resolved by Day 07. 

870.2500 Acute Dermal Irritation (Rabbit) 44731810 No irritation was noted IV 

44731811 The chemical is a strong dermal sensitizer: 

All sites challenged with test material had 

870.2600 Dermal Sensitization (Guinea Pig) 44731812 scattered mild redness to intense redness and NA 

swelling; two sites had subcutaneous 

hemorrhaging. 

Page 6 of 13 
T OXlCO og1ca I POD s U se d fi or Ri s k A ssessment 

Table 3.3. SuDUDary ofToDcological Doses and EadpoiDu for Zo:umide for Use in Oecupational Human 

Health Risk Assess~~~e~~ua 

RID, PAD, 

Exposure/ Point of Uncertainty/ Level of 

Scenario Departure FQPA Safety Concern for Study and Toxicological Effects 

Factors Risk 

Assessment 

Dermal 

Short-Term 

(1 -30 days) A toxicity endpoint was not identified. 

and Systemic toxicity was not seen in 28-day dermal toxicity in rats at the limit dose ( 1000 

Intermediate mg/kg/day). There are no concerns for developmental or reproductive toxicity or neurotoxicity. 

-Terms (l-6 

months) 

Inhalation 

Short-Term Chronic Toxicity- Dog 

(1 -30 days) NOAEL = UFA =lOX 

LOAEL = 255 mg/kglday 

and 48 UFH= lOX LOC = 100 Based on body weight changes, increases in liver 

Intermediate mg/kg/day and thyroid weights, and increases in alkaline 

-Terms (1-6 phosphatase. 

months) 

Cancer (oral, Classification: "Not likely to be Carcinogenic to Humans" based on data showing lack of 

dermal, treatment-related increase in tumor incidence 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 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). LOC = level of concern. 

Absorption 

A dermal absorption factor is not used in this assessment because a dermal toxicity POD is not 

identified based 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 is assumed to be 

equivalent to oral absorption; thus, an inhalation absorption factor is not necessary. 

Body Weight 

The standard body weight for the general population (80 kg) is used for all exposure 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 of Proposed 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 soil 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 ail A 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 of 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 pesticide 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 of the 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 inhalation 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 of a 

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 ofl3 
5.2 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, 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, 20103. 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 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 distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

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

that can potentially be used, occupational handler exposure is expected from the 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 

formulation 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 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: 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 I 09meeting.hnnl 

Page 9 of 13 
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 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 or Amount 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 

days to six months as intermediate-term. Exposure duration is determined by many things, 

including the exposed population, the use site, the pest pressure triggering the use of the 

pesticide, and the cultural practices surrounding that use site. For most agricultural uses, it is 

reasonable to believe that occupational handlers will not apply the same chemical every day for 

more than a one-month time frame; however, there may be a large agribusiness and/or 

commercial applicators who may apply a product over a period of weeks (e.g. completing 

multiple applications for multiple clients within a region). For 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 used to estimate 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 inhalation 

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. go v/pesticides/science/hand ler-exposure-data.htm I 

Page 10 of13 
cockpit) data are available to assess risks 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 of the 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 Baseline Inhalation 

lnhalation Maximum Treated or 

Unit 

Application Amount 

Exposure Scenario Crop or Target• Exposureb Rate• Handled Do see MOEr 

Dailyd 

glib ai lb ail A Acres mg/kg/day 

STilT 

LOC = 100 

Mixer/Loader 

Mixing/Loading Dry Flowables for Typical Field Crops 0. 17 350 0.0065 1 7,400 Aerial and Cbemigation Application 

Mixing/Loading Dry Flowables for 8.96 

Groundboom Application Typical Field Crops 0.17 80 0.00149 32,000 

Applicator 

Applying Sprays for Aerial Typical Field Crops 0.068 0.17 350 0.0000494 970,000 Application 

Applying Sprays for Groundboom Typical Field Crops 0.34 0.17 80 0.0000565 850,000 Application 

Mixer/Loader/Applicator 

MIUA Dry Flowables for Typical Field Crops 0.017 1000 Mechanically-Pressurized Handgun 3.9 0.000809 59,000 

Sprayers (Foliar) lb ai/gal gallons 

a "Typtcal Fteld Crops" tnclude bulb vegetables (Group 3-07). 

b Based on the "Occupational Pesticide Handler Unit Exposure Surrogate Reference Table" (March 2012); Level of mitigation= Baseline 

except for aerial applicator which includes engineering controls. 

c Based on the maximum application rates on the proposed labels (Reg. No. 10163-6414, Gavel® 75DF Fungicide). 

d Exposure Science Advisory Council Policy #9.1. 

e Inhalation Dose= Dermal Unit Exposure (Jlg/lb ai) x Conversion Factor (0.001 mgfJlg) x Application Rate (lb ai/acre or gal) x Area Treated or 

Amount Handled Daily (A or gal/day) + BW (80 kg). 

f Inhalation MOE= Inhalation NOAEL (48 mgfkgfday) + Inhalation Dose (mgfkgfday). 

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 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. In addition, the timing of pesticide applications, 

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

Page 11 of 13 
An 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 

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, 20106

. 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 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 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 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 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/scipoly/SAP/meetings/2009/ 120 I 09meeting.html 

Page 12 of 13 
Appendix 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 scenario (mg ailkg/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: 

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 scenario (mg ai/kg/day). 

Page 13 of 13