Date: 

Subj ect: 

UNITED STATES ENVIRONMENT AL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

December 03, 20 15 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Hymexazol: Occupational and Residential Exposure Assessment for Seed 

Treatment Uses on Sugar Beets in Support of Registration Review. 

PC Code: 129107 

Registr ation Nos.: 348210-1 

Petition No.: NA 

DP Barcode: 0429298 

Decision No.: 4°!Vc/I 

Regulatory Action: Section 3 

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

TXR No.: NA CAS No.: 10004-44-1 

MRID No.: NA 40 CFR: NA 

From: 

Through: 

To: 

Matthew Lloyd, CIH; Industrial Hygienist 

Risk Assessment Branch VII 

Health Effects Division (7509P) • -/ oti. 

Michael 

Risk Assessment 

Metzger, 

Branch 

Chief . 

«'~

~~ I (~B57) Health Effects Division (7509P) 

and 

Kristin Rury, Biologist '{-.~ a/ A11J- Gerad Thorton, Environmental. ;rote~Specialist )JJ'fl \ 

Exposure Science Advisory Committee (ExpoSAC) 

I Jealth Effects Division (7509P) 

Caitlin Newcamp, Chemical Review Manager 

& 

Tom Moriarty, Team Leader 

Risk Management and Implementation Branch I 

Pesticide Re-Evaluation Division (7508P) 

The Pesticide Reevaluation Division (PRO) requested that the Health Effects Division (HED) 

conduct an exposure and risk assessment for the existing registration of hymexazol. The only 

registered use of hymexazol is as a sugar beet seed treatment and there is only one actively 

registered end-use product: EPA Reg. No. 482 10-1 . Because hymexazol is only a commercial 

seed treatment, non-occupational exposure is not expected. 

Page 1 of 17 
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 ExpoSAC 

Poli cies 14/ 15. J (SOPs for Seed Treatment); . 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 October 15th, 20 15. 

Page 2 of 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 

3.0 Hazard Characterization ..... .................................................................................................. 7 

4.0 Use Profile .. ............................ .............................................................................. .... ........... 9 

5.0 Residential Exposure and Risk Estimates .......................................................................... I 0 

6.0 Non-Occupational Spray Drift Exposure and Risk Estimates ........................................... I 0 

7.0 Residential Bystander Post-Application Inhalation Exposure .................................... I 0 

8.0 Occupational Exposure and Risk Estimates ...................................................................... I I 

8.1 Occupational Handler Exposure/Risk Estimates ... ................ .... .... ..................... ........ .... 11 

6.2 Occupational Post-application Exposure/Risk Estimates .. ............... ....... ........... ........ ... 16 

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

Page 3 of 17 
1.0 Executive Summary 

Hymexazol is the International Organization for Standardization (ISO) common name for 5-

methylisoxazol-3-ol or 5-methyl-1 ,2-oxazol-3-ol (International Union of Pure and Applied 

Chemistry, or IUPAC name). Hymexazol is a systemic fungicide for control of fo li ar and soilborne plant diseases. There is an existing registration only as a seed treatment use for sugar 

beets. As a wettable powder intended for commercial seed treatment, the maximum application 

rate is for standard pelletization, at the rate of 45 to 90 grams of TACH I GAREN® 70 WP per unit 

of I 00,000 seeds (approx. I kilogram of raw sugar beet seed). Hymexazol may be applied only 

using commercial seed treatment equipment. Based on the existing seed treatment registration 

(sugar beet), occupational handler is expected for the short- and intermediate-term for primary 

handlers treating seed, and for secondary handlers who plant the seed. 

According to the current product labeling, Applicators and mixer/loaders who handle 

hymexazol, such as at commercial seed treatment facilities, must wear long-sleeved shirt and 

long pants, chemical-resistant gloves made from any waterproof material, shoes plus socks, 

protective eyewear, and in the absence of adequate ventilation or dust control systems, a nonpowered air purifying respirator equipped with a R- or P- series filter. 

Baggers and other persons who handle treated seed, such as at commercial seed treatment 

faci lities, must wear long-sleeved shirts and long pants, shoes plus socks, and protective 

eyewear. 

Hazard Characterization 

Technical hymexazol shows low acute toxicity by the oral, dermal, and inhalations routes of 

exposure (Toxicity Category llf); although it is a severe ocular irritant (Toxicity Category I). 

Hymexazol is classified as a Toxicity Category llI for dem1al irritation and is not a dermal 

sensitizer. 

For assessment of occupational handler exposures, a short- and intermediate-term no observed 

adverse effect level (NOAEL) of 31 mg/kg/day was selected for dermal and inhalation exposure 

assessment based on an increase in post-implantation loss and a decrease in litter size at the 

lowest observed adverse effect level (LOAEL) of 159 mg/kg/day from a developmental study in 

rats. Since no dermal absorption data are available and the physiochemical data could not be 

used to estimate the dermal absorption factor (DAF), toxicity via the dermal route was 

considered to be equivalent to toxicity by the oral route of exposure (I 00% demial absorption). 

Since no inhalation data are available, toxicity by the inhalation route is considered to be 

equivalent to toxicity by the oral route of exposure. Also, since the POD selected for dermal and 

inhalation exposures was based on developmental effects, the body weight appropriate for 

dennal and inhalation assessments is 69 kilograms. Per HED's HASPOC Committee, the 

requirement for a subchronic inhalation toxicity study was not waived (HASPOC; TXR 

0057244). 

In accordance with the Agency's 2005 Guideline for Carcinogen Risk Assessment, hymexazol is 

classified as "Not Likely to be Carcinogenic to Humans." The Agency has determined that the 

quantification of risk using a non-linear approach (i.e., RID) is protective of carcinogenicity. 

Page 4 of 17 
FQPA and Uncertainty Factors 

The level of concern (LOC) for all occupational scenarios is an ARI of < I ; Since the 

toxicological effects from the dermal and inhalation studies are common, these routes are 

combined for the purposes of occupational exposure assessment. There are no non-dietary nonoccupational exposure scenarios anticipated for hymexazol where the FQPA safety factor 

applies. 

Residential Exposure 

The existing use pattern does not result in residential exposures, and therefore, there are no 

existing residential uses re-eva luated in this document. 

Occupational Handler Exposure 

Based on the proposed use pattern, short- and intermedi ate-term durations of exposure are 

expected for occupational handlers. The estimates of exposure to pesticide seed treatment 

handlers (treatment and planting) are based upon ExpoSAC Policies 14 & 15 and a memorandum 

from the Biological and Economic Analysis Division (BEAD), "Acres Planted Per Day and 

Seeding Rates of Crops Grown in the United States" (J. Becker, March 201 1 ). 

The maximum single application rate for sugar beet seed treatment is the "standard pellet" 

scenari o. A lower application rate ("minimum buildup" scenario) is also an option based on the 

label, although it is rarely used in commercial seed treatment practice. Most "standard pellet"' 

occupational handler scenarios are not of concern (based on the Aggregate Risk Index [ARI] 

LOC of I) with label-specified PPE. However, for the handler mixing the wettabl e powder, the 

use of engineering controls (i.e., water soluble packets) is required to reach acceptable MO Es (an 

ART > 1). 

Occupational Post-application Exposure 

The potential for dermal post-application exposures following the planting of hymexazol-treated 

seeds is unlikel y because no routine cultural practices involve sustained levels of contact with 

treated seed after it has been placed in the soil or other planting media. 

Commercial treatment of seeds is not within the scope of the Worker Protection Standard. 

Hymexazol is not registered for non-commercial seed treatment and does not require Worker 

protection Standard labeling. 

Similarly, a post-application inhalation exposure assessment is not required as exposure is 

expected to be negligible. However, the seed treatment handler assessments provide quantitative 

inhalation exposure assessments for seed treaters and planters, both of which have inhalation 

MO Es that well exceed the LOC and would be protective of post-application inhalation exposure 

scenanos. 

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 I.I (PHED I.I); ExpoSAC Policy 14 and 15. 1 (SOPs for 

Page 5 of 17 
Seed Treatment); are (I) subject to ethics review pursuant to 40 CFR 26, (2) have received that 

review, and (3) are compliant with applicable ethics requirements. For ce1iain 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 

2.1 Summary of Risk Estimates 

The results of the occupational handler exposure and risk assessment indicate that at label 

specified PPE some "standard pellet" (i.e., maximum single application rate) scenarios represent 

risk estimates of concern. Where risk concerns exist, the combined risk estimates are driven by 

dermal exposure. With the label defined PPE, risk estimates of concern were identified for the 

fol lowing "standard pellet" scenarios: 

• Mixer (wettable powder) - combined ARI of 0.22 

• Multiple Activities (w/o gloves) - combined ARI of 0.87 

Combined risk estimates for the wettable powder mixer scenario remains of concern with the 

addition of double layer dennal PPE (ARI of 0.23) and exceed the ARI LOC of 1 onl y when 

engineering controls (i.e., water soluble packets) are considered. The multiple activities (w/o 

gloves) scenario has a combined ARI below I (0.87) because the dermal MOE is 97. The 

addition of gloves to the scenario increases the dermal MOE to 310 and the ARI to 2.2 

For occupational post-appli cation exposures, because of the nature of the seed treatment uses, a 

quantitative assessment was not conducted as exposures are adequately addressed by WPS 

provisions. 

2.2 Label Recommendations from Occupational Assessment 

The occupational handler scenarios associated with the "standard pellet" directions on the 

product labe ls may require risk mitigation to address risk estimates of concern associated with 

label-specified PPE and application rates. Additionally, the label specifies the use of "adequate 

ventilation or dust control systems" on the product label. HED recommends that additional detail 

be added to avail able product labeling to delineate when respiratory protection is needed for 

occupational handlers. The multiple activities (w/o gloves) scenario is below an ARl of 1 (0.87), 

although it is because the dermal MOE (w/o gloves) is 97. The addition of gloves to the 

multiples activities scenario increases the ART to 2.2. 

Commercial treatment of seeds is not within the scope of the Worker Protection Standard. 

Hymexazol is not registered for non-commercial seed treatment and does not require Worker 

Protection Standard labeling. 

1 hnp://-.vww.cpa.gov/pesticides/sciencc/handler-cxposure-data.hrml and 

http://www.cpa.gov/pesticides/science/posr-app-exposurc-data.html 

Page 6 of 17 
3.0 Hazard Characterization 

Hymexazol is an oxazole fungicide that limits fungi growth thro ugh inhibitio n of RNA and DNA 

synthesis. In mammals, the adverse effects of hymexazol exposure were most apparent with in 

utero exposure. Developing rodents were the most susceptible population to hymexazol 

treatment, demonstrating increased sensitivity at doses below that required to elicit maternal 

toxicity. Of the adult animals, dogs were the most sensitive to hymexazol exposure. Subchronic 

oral exposure targeted the thyroid leading to increased absolute and relative thyroid weight 

accompani ed by minimal increase in epithe lial height and minima l to moderate thyroid epithelial 

hyperplasia. Neurological effects, decreased brain weight and cerebral length in males, were 

equi vocal and occurred around the limit dose. The respiratory system was unaffected in oral or 

dermal exposures and was minimally tox ic in acute inha lation exposures (Category III). The 

immune system was similarly unaffected after oral exposure up to the limit dose. 

Hymcxazol shows low acute toxicity by the oral, dermal, and inhalations routes of exposure 

(Toxicity Category III), although it is a severe ocular irritant (Toxicity Category I). Hymexazol is 

classified as a Toxicity Category JV for dermal irritation and is not applicable for skin 

sensiti zation. A summary of the acute toxicity for hymexazol is provided in Table 3. 1. 

Table 3.1 Acute Toxicity Profile - Hymexazol 

Guideline No. Study Type MRID(s) Results Toxicity Category 

870.1100 Acute oral [rat] 42960008 LDso= Ill 

M = 1600 mg/kg 

F = 1700 mg/kg 

Both = 1.7 g/kg 

870.1100 Acute oral [mouse] LDso = 1700 

mg/kg 

870.1200 Acute dermal [rat] 42960009 LDso > 2000 Ill 

mg/kg 

870.1300 Acute inhalation [rat] 429600 10 LCso > 0.65 mg/L Ill 

4 hour, aerosol, 

whole body 

870.2400 Acute eye irritation [rabbit] 42960011 Severe ocular I 

irritanr/Severe 

corneal opacity w/ 

hyperaemic blood 

vessels 

870.2500 Acute dermal irritation [rabbit] 4299730 1 Non-irritant IV 

870.2600 Skin sensitization [guinea pig] 42960012 Sensitizing NIA 

(MagnussonKligman 

maximization test) 

For assessment of occupational handler exposures, a short- and intermediate-term no observed 

adverse effect level (NOAEL) of 3 1 mg/kg/day was selected for dermal and inhalation exposure 

assessment based on an increase in post-implantation loss and a decrease in litter size at the 

Page 7 of 17 
lowest observed adverse effect level (LOAEL) of 159 mg/kg/day from a developmental study in 

rats. 

A dennal absorption study was not submitted for hymexazol; therefore, a conservative dermal 

absorption factor of I 00% was used in lieu of an empirically derived value. The physicochemical 

data and endpoints from the guideline studies could not be used to estimate the dermal 

absorption factor (OAF). A clear LOAEL was not reported for the dermal study and could not be 

compared to LOAEL established in the oral study. A IOOx UF (I Ox to account for interspecies 

extrapolation and 1 Ox for intraspecies variation) was applied to the NOAELs for dermal 

exposures. 

In the absence of a route specific study, the offspring NOAEL from the two general reproduction 

study was used for the short- ( 1-30 days) and intermediate-term (l-6 months) inhalation 

exposures. Absorption from inhalation was assumed to be equivalent to an oral exposure. A 

1,000x UF ( 1 Ox to account for interspecies extrapolation and 1 Ox for intraspecies variation along 

with a 1 Ox factor to account for a missing inhalation study) was applied to the NOAELs for 

inhalation exposures. Since no inhalation data are available, toxicity by the inhalation route is 

considered to be equi valent to toxicity by the oral route of exposure. Note: the requirement for a 

subchronic inhalation toxicity study was not waived (HASPOC, TXR 0057244). 

There is a paucity of evidence linking hymexazol to a carcinogenic and mutagenic mode of 

action. Rats and mice exposed to hymexazol at high doses (> 500 mg/kg/day) for two years did 

not develop neoplasti c tumors and no signs of mutagenicity were reported in gene mutation, 

mouse lymphoma, or micronucleus assays. In accordance with the Agency's 2005 Guideline for 

Carcinogen Risk Assessment, hymexazol is classified as "Not Likely to be Carcinogenic to 

Humans." 

HED has applied the traditional uncertainty factors of I OX for inter-species extrapolation and 

I OX for intra-species variability. Exposure routes are combined because toxic effects are 

common between the inhalation and dermal routes of exposure. A total aggregated risk index 

(ARI) was used since the LOC values for dermal exposure ( 100) and inhalation exposure (I 000) 

are different. 

A summary of the toxicological doses and endpoints for occupational and residential exposure 

scenarios is provided in Table 3.2. 

Table 3.2. Summary of Toxicological Doses and Endpoints for Hymexazol for Use in Occupational Human 

Hea lth Risk Assessments 

Level of 

Concern for 

Exposure/ Point of Uncertainty Risk 

Scenario Departure Factors Assessment Study and Toxicological Effects 

Dermal UFA= !Ox 2-gcneration reproduction -rat Short-and NOAEL = 3 1 

Intermediate- mg/kg 

UFH= IOx LOC = JOO LOA EL= I 59 mg/kg based on increase in 

Tenn post-implantation loss. decrease in litter size 

Inhalation UF"= !Ox 2-gcneration n.:production -rat Short- and NOAEL = 3J UF11=10x 

Intermediate- mg/kg UFoo= IOx LOC = 1,000 LOA EL = I 59 mg/kg based on increase in 

Tem1 post-implantation loss, decrease in litter size 

Page 8 of 17 
Table 3.2. Summa ry of Toxicological Doses and Endpoints for Hymexazol fo r Use in Occupational Human 

Health Risk Assessments 

Level of 

Concern for 

Exposure/ Point of Uncertainty Risk 

Scenario Departure Factors Assessment Study and Toxicological Effects 

Hymexazol is not carcinogenic in long term studies with rats and mice and not mutagenic in 

Cancer (dermal the gene mutation, mouse lymphoma, and micronucleus assays. In accordance with the 

and inhalation) Agency's 2005 Guideline for Carcinogen Risk Assessment, hymexazol is classified as "Not 

Likely to be Carcinogenic to Humans''. 

Pomt of Departure (POD) =A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOA EL = no observed adverse effect level. LOA EL = lowest observed adverse effect level. 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. NIA = not applicable. 

4.0 Use Profile 

Hymexazol is a fungicide used in seed treatment for control of seedling diseases caused by 

Aphanomyces spp. and Pythium spp. in sugar beets. There are no existing registrations for 

agricultural or residential use sites. 

Commercial seed treatment facilities may use the hymexazol wettable powder (WP) formul ation 

in commercial seed treatment processing to apply hymexazol as either a standard pellet or a 

minimum pellet build up. In either case, hymexazol must be used with an EPA approved dye that 

imparts an unnatural color to the seed. 

Federal Law requires that bags containing treated seeds shall be labeled with the fo llowing 

information. "This seed has been treated with Hymexazol fungicide. Do not use for feed, food or oil 

purposes. Store away from feeds and foodstuffs." 

For Application as a standard pellet: Apply as a commercial seed treatment on pelleted sugar beet 

seeds at the rate of 45 to 90 grams of TACH !GAREN® 70 WP per unit of I 00,000 seeds (approx. I 

kilogram of raw sugar beet seed). Seed must be pelleted at a minimum weight to weight ratio of2: I 

pelleting mixture to raw seed. 

For Application as a minimum build-up pellet: Apply as a commercial seed treatment on 

minimum build-up pelleted sugar beet seeds at the rate or20 to 30 grams ofTACHIGAREN® 70 

WP per unit of I 00,000 seeds (approx. I kilogram of raw sugar beet seed). Seed must be pelleted at a 

minimum weight to weight ratio of3 :10 pelleting mixture to raw seed. 

The existing labeling restri cts use of hymexazol "on agricultural establ ishments in hopper-box, 

planter-box, slurry-box or other seed-treatment applications at or immediately before planting." 

Commercial seed treatment uses are registered for sugar beet, and the one wettable powder 

(WP) formulation can be applied using only commercial seed treatment equipment. The 

existing use pattern is outlined below in Table 4.1 . 

Page 9 of 17 
Table 4.1. Summary of P roposed Commer cial Seed Trea tment Uses of Hymexazol 

Formul:llion Use Directions and !EPA Reg. No.I Crop Max Applkation Ratcb Limitations Trade Name• 

• 90g/100.000 

seeds 

. Seed must be 

70% TACHIGAREN® 70 pelleted at a 

WP Sugar beet 90 g product I kg seed 0.056 lb ai/lb seed minimum 

148210-1] Standard pellet weight to 

weight ratio of 

2: I pelleting 

mixture to raw 

seed. 

. 30g/l 00.000 

seeds 

• Seed must be 

70% TACH lGAREN® 70 Sugar beet pelleted at a 

minimum WP Minimum build up 30 g product I kg seed 0.02 1 lb ai/lb seed weight to [-1821 0-11 pellet weight ratio of 

3: 10 pelleting 

mixture to raw 

seed 

• Fomrnlation codes: WP = wettable powder. 

b As registered rates are given as "mass ai per seed", a seed count(# seeds per pound) is needed to convert to "mass 

ai per pound seed" for the purposes of estimating exposure. Based on the BEAD memo "Acres Planted Per Day 

and Seeding Rates of Crops Grown in the United States" (J. Becker, March 2011), the following seed count 

conversions were used to convert lb ai/seed rates into lb ai/lb seed: sugar beet - 40,000 seeds per pound. 

5.0 Residentia l Exposure and Risk Estimates 

The ex isting seed treatment use of hymexazol are not expected to result in residential (nonoccupational non-dietary) exposures. Therefore, no quantitative assessment has been completed 

for handlers or post-application scenarios. As there are no residential uses assessed, there is no 

residential contribution to the aggregate risk assessment. 

6.0 Non-Occupational Spray Drift Exposure and Risk Estimates 

Spray drift is a potential source of exposure to those nearby pesticide applications. Where 

appropriate, 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. r n the case of hymexazol, the only registered use site is commercial seed 

treatment. Planting pelleted seed treated with hymexazol is not anticipated to result in spray 

drift. 

7.0 Residential Bystander Post-Application Inhalation Exposure 

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP's final report on 

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/1 20 109meeting.html). The 

agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

Page 10 of 17 
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 

hymexazol. 

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. 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 protective gear or controls used by a handler can cause exposure levels 

to differ in a manner specific to each application event. 

Based on the existing seed treatment registration (sugar beet), occupational handler exposure is 

expected. Occupational seed treatment handlers may experience short- and intermediate-term 

exposure to hymexazol while performing seed treatment activities in commercial settings. In 

addition, occupational handlers may experience short- and intermediate-term exposure while 

planting hymexazol-treated seeds (for the purposes of seed treatment risk assessment, planting 

treated seeds are referred to as 'secondary handlers'). 

Treating Seed (Primary Handler) 

Potential occupational exposure scenarios from the use of hymexazol as a commercial 

seed treatment include: mixing, loading, applying wettable powder formulations; bagging 

treated seed; sewing bags; and multiple activities. Typically, for large-scale commercial 

seed treatments, workers perform only those specific individual tasks listed above; 

however, it is assumed that workers also may perform multiple activities throughout the 

day. As a result a "multiple activities" scenario (i.e. where one worker performs all seed 

treatment tasks such as loading/applying, sewing, bagging, cleaning, calibration, repair, 

forklift driver, etc.) was addressed. 

Planting Treated Seed (Secondary Handler) 

Potential occupational exposure scenarios from the use of hymexazol as a commercial 

seed treatment include planting treated seed (secondary handler). Planting treated seed 

consists of the farmer purchasing bags of treated seed, placing the seed in the hopper and 

applying seed to fields. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios: 

• Mixer - wettable powder slurry 

• Mixing/loading/applying wettable powders; 

Page 11 of 17 
• Bagging treated seeds; 

• Sewing bags with treated seeds; 

• Multiple (commercial) seed treatment activities; and, 

• Planting treated seeds. 

Occupational Handler Exposure Data and Assumptions 

Applicators and mixer/loaders who handle hymexazol, such as commercial seed treatment 

facilities, must wear long-sleeved shirt and long pants, chemical-resistant gloves made from 

any waterproof material, shoes plus socks, protective eyewear, and in the absence of adequate 

ventilation or dust control systems, a non-powered air purifying respirator equipped with a Ror P- series filter. Baggers and other persons who handle treated seed, such as commercial seed 

treatment facilities, must wear the same protection as applicators and mixer/loaders minus the 

chemical resistant gloves. 

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. 

Exposure Duration 

Treatment of the proposed seeds is expected to result in short- and intermediate-term exposure. 

However, since the same dermal and inhalation endpoints were selected for short- and 

intermediate-term exposure durations, and the assessment is protective of both exposure 

durations. 

According to a survey by the Agricultural Handlers Exposure Task Force (AHETF, 20 I 0) com 

commercial facilities operate 240 days per year (501h percentile; range 150 to 270 days), canola 

commercial faci lities operate 180 days per year (50111 percentile: range 90 to 2 10 days) and 39% 

of soybean is treated downstream for a duration of 49 days (50111 percentile; range 4 to 150 days), 

while soybean commercial facilities operate 210 days per year (501

h percenti le; range I to 270 

days). No information is available on sugar beet seed treatment. While these durations would be 

considered to potentially exceed the typical intermediate-term duration used in HED's 

occupational assessments, HED had no information to indicate that the same chemical is used 

consecutively for a long-term duration. Therefore, chronic occupational handler exposure for 

seed treatment was not assessed. 

Application Rate 

Refer to the proposed use pattern table in Section 4.0. Table 6.1.1 shows the risk estimates for 

the maximum single application rate (i.e., the "standard pellet"). The standard pellet rate that is 

assessed is protective of the lower application rate (i.e., minimum buildup) identified in Section 

4.0. 

Unit Exposures 

Page 12of17 
It is the policy of HED to use the best available data to assess handler exposure. Chemicalspecific data for assessing exposure during commercial seed treatment and seed planting were 

not submitted to the Agency in support of this Registration Review action. Unit exposures are 

derived from: 

1) mixing/loading well able powders - September 20 I 5 Occupational Pesticide Handler Unit 

Exposure Surrogate Reference Table (M/ L wettable powders) 

2) all other occupational handler scenarios - ExpoSAC Policy 14: SOPs for Seed Treatment 

(May 1, 2003), which are based on data for open mixing/loading/application systems. 

Amount Handled 

HED is currently in the process of revising ExpoSAC Policy 15: Amount of Seed Treated or 

Planted per Day (March 2, 2004) in efforts to update the dai ly amount of seed treated in 

commercial seed treatment facilities. With the increasing demand for hybridized treated seeds, 

there have been modifications not only in the seed treatment equipment, but in the market shares 

of new and currently registered pesticide products. HED understands that due to the high cost of 

producing hybrid seeds, direct seeding is done in a precise manner which requires lower volumes 

of seed per acre. However, this does not provide a direct correlation to the amount of seed which 

is treated in the commercial seed treatment facilities. 

The amount of seed handled (for both primary/treater and secondary/planter handlers) is based 

on HED ExpoSAC Policy 15, HED ExpoSAC Policy SOP 15.1 , and the BEAD memo: "Acres 

Planted Per Day and Seeding Rates of Crops Grown in the United States." In some cases, the 

amount of seed planted per day is a conservative calculation based on a low amount of seeds per 

pound and a high amount of seeds planted per acre (e.g., for sugar beets: 435,600 seeds/acre -;-

40,000 seeds/lb * 80 acres planted per day = 870 lbs seed). 

The amount of seed treated per day at a commercial facility is summarized below for sugar beets. 

Amount of Seed 

Crop/Seed Treated per Day Source 

(lb)B 

ExpoSAC Policy 15. l 

Sugar beet 3,000 ("General infonnation from a small number of facilities (exact 

number not reported) that film-coat small seeded vegetables was 

collected by the AH ETF (20 10). ") 

• Estimates are based on short-term/ intermediate-term durations. 

The amount of seed planted per day is summarized below for each crop. 

Amount of Seed 

C rop/Seed Pla nted per Day Sou rec/Calculation 

(lb) 

435,600 seeds/acre + 40,000 seeds/lb • 80 acres planted/day 

Sugar beet 870 • 435,600 seeds/acre: Table I 0, BEAD memo 

• 40,000 seeds/lb: Table B-1 , BEAD memo 

• 80 acres planted per day: ExpoSAC Policy 15 

Page 13 of 17 
Mitigation/Personal Protective Equipment: To reflect the registered registration, estimates of 

dermal and inhalation exposure were calculated for "baseline" - defined as a single layer of 

clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no chemical-resistant 

gloves, and no respirator. 

Additional dermal and inhalation exposure estimates were calculated where potential risk 

concerns were identified. For example, the mixer scenario for commercial seed treatment was 

also evaluated with double layer denn al PPE plus chemical-resistant gloves. 

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations 

The algorithms used to estimate non-cancer exposure and dose for occupational handlers can be 

found in Appendix A. 

Combining Exposures/Risk Estimates 

Exposure routes are combined because toxic effects are common between the inhalation and 

dernrnl routes of exposure. A total aggregated risk index (ARI) was used since the LOC values 

for dermal exposure (I 00) and inhalation exposure ( 1000) are different. The target ARI is 1; 

therefore, AR ls of less than I are risk estimates of concern. The aggregate risk index (ARI) was 

calculated as follows. 

Aggregate Risk Index (ARI)= /.:,- [(Dermal LOC + Dermal lv!OE) + (/nha/atio11 LOC .:,- fnhalation J\1/0£)) 

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates 

Occupational handler risk estimates are presented below in Table 8.1. l . The occupational 

handler risk estimates are presented for the "standard pellet" application scenario (the higher 

application rate). 

The results of the occupational handler exposure and risk assessment indicate that short- and 

intermediate-term combined dermal and inhalation risk estimates exceed HED's LOC in some 

cases. Where risk concerns exist, the combined risk estimates are driven by dermal exposure, and 

with the label defined PPE, risk estimates of concern were identified for the following "standard 

pellet" scenarios: 

• Mixer (wettable powder) - combined ARI of 0.22 

• Multiple Activities (w/o gloves) - combined ARI of 0.87 

Overall, dermal MO Es range from 97 to 1,800 for seed treaters (LOC = I 00). The multiple 

activities (w/o gloves) scenario has a combined ARI below 1 (0.87) because the dermal MOE is 

97. Inhalation MOEs range from 300 to 70,000 for seed treaters (LOC = 1,000). Combined risk 

estimates for the wettable powder mixer exceed the ARI LOC of I only when engineering 

controls (i.e., water soluble packets) are considered. 

Page 14 of 17 
Table 8.1.1 Summa ry of Short- and Intermediate-Term Handler Exposures and Risks for Hymexazol Seed 

Treatment 

Max Unit Exposure2 Amount Absorbed Dose Applicati of Seed MOE5 

Seed Type on Ra te1 (mg/lb ai) Treated3 (mg/kg/day)4 

Total ARl 6 

lsuga rbeet) lb ai/lb lb Dermal Jnhal. 

seed Dermal In ha I. 

seed/day 

Dermal lnhal. (LOC= (LOC= 

100) 1,000) 

Mixer - Wettable Powder (single layer, gloves, no respirator) 

Standard 0.056 0.170 0.0434 3,000 0.4 1 0.1 04 76 300 0.22 Pellet 

Mixer - Wettable Powder (double layer, gloves, PFS respirator) 

Standard 0.056 0.130 0.0434 3,000 0.3 1 0.1 04 100 300 0.23 Pellet 

Mixer - Wettable Powder (double layer, gloves, no respirator) 

Standard 0.056 0. 130 0.00868 3,000 0.31 0.021 100 1500 0.6 Pellet 

Mixer - Wettable Powder (water soluble packets, no respirator) 

Standard 0.056 0.0098 0.0002 3,000 0.023 0.001 1300 54,000 10.S Pellet 4 

LOADER/APPLICATOR (single layer, gloves7) 

Standard 0.056 0.023 0.0003.t 3,000 0.055 0.001 560 38,000 4.9 Pellet 

SEWER (single layer, no gloves) 

Standard 0.056 0.0062 0.00023 3,000 0.0 173 0.0006 2, 100 56,000 15.3 

Pe llet 

BAGGER (s in~le layer, no gloves) 

Standard 0.056 0.009 1 0.000 16 3,000 0.02532 0.00045 1,400 8 1,000 I 1.9 

pellet 

MUL TrPLE ACTIVITIES (combina tion of loader/applicator without gloves'+ no coveralls, 

sewer without gloves, stacker without gloves) 

Standard 0.056 0.134 0.00 16 3,000 0.320 0.0038 97 8. 100 0.87 pellet 

M UL TrPLE ACTIVITIES (combination of loader/applicator with gloves7 + no coveralls, sewer with gloves, 

stacker with !!loves) 

Standard 0.056 0.042 0.001 6 3,000 0. 100 0.0038 3 10 8, 100 2.2 pellet 

I Applica1ion Rates based on existing label uses for hymcxazol (sec Table 4.1 ). 

2 Unit Exposures from HED Exposure Science Advisory Council Policy 14. 

3 1 IED default for lb seed lrcmed per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the 13EAD memo "Ac s Planted 

Per Day and Seeding Raics of Crops Grown in lhe United States" (J. Becker. March 20 11 ). 

4 Daily Absorbed Dose (mg/kg/day)= daily unit exposure (mg/lb ai) >< application rate (lb ai/lb seed) >< amount treated (lb seed/day) >< Absorp1io11 

(100% for dem1al, 100% for inhalation) + body wcigh1 (69 kg adult female for dermal exposure due to sex-specific toxicity; 

5 MOE = NOAEL (dcm1al = 31 mg/kg/day for shon- and intermediate-term exposure: inhalation= 31 mg/kg/day for shon- and intcrrnediatc-tcm1) 

... Absorbed Dose (mg/kg/day). LOC = I 00. 

6 ARI "' Aggregate Risk Index = I+ [(Demial LOC + Dcnnal MOE)+ (Inhalation LOC + Inhalation MOE)]. 

7 Available data represents workers wcarinl! chcmical-resis1m11 gloves and other label-represented PPE. 

Table 8.1.2. Summary of Secondary Handler (Planter) Exposure and Risk Estimates for Hymcxazol (Single 

Laver, Gloves during Loading Only). 

Seed Max Unit Exposureb Amount Absorbed Dose Application of Seed MOE• Total ARI' Type Rate' (mg/lb ai) Planted (mg/kg/day) d 

Page 15 of 17 
Per 

Daye 

lb Dermal lnbal. 

lb ai/lb seed Dermal lnhal. seelfl<lay Dermal Inhal. (LOC = (LOC = 

100) 1,000) 

Standard 0.056 0.25 0.0034 87 1 0. 174 0.0024 180 13,000 1.6 Pellet 

a Applicauon Rates based on proposed label uses for hymcxa/ol (see Table 4. 1 ). 

b Unit Exposures from 111!0 Exposure Science Advisory Council Policy 14: Standard Opera1ing Procedures for Seed Treatment Available data 

rcprcscnls workers wearing chc111ical·rcsis1ant gloves. Unit exposures rcprcsen1ing workers withoul chc111ical-rcsis1an1 gloves were calculated 

by increasing exposure to 1he hands-only portion of 1hc total dermal exposure measurcmcni assuming chemical-resistant gloves provide 90% 

pro1cc1ion (i.e., dividing non-gloved hand exposures by 0.1 ). the standard prolcction fac1or assumption for chemical-rcsis1an1 gloves. 

c 1 IED dcfaull for lb seed pla111cd per day for sugar beels from HED Exposure Science Advisory Council lnlerim Policy 15 and the BEAD 

memo ··Acres Pla111cd Per Day and Seeding Ra1es of Crops Gro11n in the Uniled S1a1es·· (J. Becker, March 2011). 

d Daily Absorbed Dose (mg/kg/day)= daily unil exposure (mg/lb ai) >< applica1ion r:ue (lb ai/lb seed) ~ amounl trealcd (lb seed/day) x 

Absorp1ion (100% for demial, 100% for inhala1ion) + body weigh! (69 kg). 

e MOE = NOAEL (dermal = 31 mg/kg/day for short- and in1crmcdia1c-1ern1 exposure: inhalalion = 3 1 mg/kg/day for short- and in1cnncdi a1c1crm) + Absorbed Dose (mg/kg/day). LOC = 100. 

f ARI= Aggregale Risk Index = I+ [(Dermal LOC + Dermal MOE)+ (lnhala1ion LOC + lnhalalion MOE)]. 

6.2 Occupational Post-application Exposur e/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. 

The potential for dermal and inhalation post-application exposures following the planting of 

hymexazol-treated seeds is unlikely because no routine cultural practices involve sustained 

levels of contact with treated seed after it has been placed in the soil or other planting media. 

Commercial treatment of seeds is not within the scope of the Worker Protection Standard. 

Hymexazol is not registered for non-commercial seed treatment and does not require Worker 

Protection Standard labeling. 

A post-application inhalation exposure assessment is not required as exposure is expected to be 

negligible. Seed treatment assessments provide quantitative inhalation exposure assessments for 

seed treaters and secondary handlers (i.e., planters). It is expected that these exposure estimates 

would be protective of any potential low-level post-application inhalation exposure that could 

result from these types of applications. 

Page 16 of 17 
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 mgl ug 

exposure (mg ai/day), 

unit exposure (μg ai/lb ai), 

maximum application rate according to proposed label (e.g., lb ai/seed or lb ai/lb 

seed), and 

area treated or amount handled (e.g., lb seed/day,# seed/day). 

The daily doses are calculated using the following formula: 

where: 

ADD 

E 

AF 

BW = 

ADD= 

E*AF 

BW 

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

exposure (mg ai/day), 

absorption factor (dermal and/or inhalation), and 

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 demrnl 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: 

where: 

MOE = 

POD = 

ADD 

POD 

MOE= -

ADD 

margin of exposure: value used by HED to represent risk estimates (unitless), 

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

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

The Aggregate Risk Index (ARI) formula (that combines dermal and inhalation doses with 

difference toxicological Levels of Concern (LOCs) is located in Section 8. 1. 

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