Page 3 of 18

Table of Contents

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

2.0 Summary of Conclusions/Data Deficiencies....................................................................... 5

3.0 Hazard Characterization....................................................................................................... 5

4.0 Use Profile ........................................................................................................................... 7

5.0 Residential Exposure and Risk Estimates............................................................................ 9

5.1 Spray Drift........................................................................................................................ 9

5.2 Residential Bystander Post-Application Inhalation Exposure ....................................... 10

6.0 Occupational Exposure and Risk Estimates ...................................................................... 10

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

6.2 Occupational Post-application Exposure/Risk Estimates .............................................. 17

6.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates...................... 17

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates.......................... 18
Page 4 of 18

1.0 Executive Summary

Fenpyrazamine is a new active ingredient fungicide that is proposed for registration in the United 

States. Fenpyrazamine is a fungicide to be used for control of gray mold (Botrytis) in berries and 

small fruits, almonds, lettuce and ornamentals. It is not systemic but there is some translocation 

in plants. Fenpyrazamine shows its fungicidal activity through inhibition of germ tube 

elongation and mycelium elongation. However, the exact biochemical mechanism of fungicidal 

activity is not currently known.

Valent U.S.A. Corporation is proposing the US registration of fenpyrazamine for uses in almond, 

small fruit climbing subgroup 13-07F, head and leaf lettuce, low growing berry subgroup 13-

07G, and ornamentals. In addition, IR-4 is proposing the use of fenpyrazamine on bushberry 

subgroup 13-07B, caneberry subgroup 13-07A, ginseng, and pistachio. The product, V-10135 4 

SC Fungicide, is a suspension concentrate formulation containing 43.6% active ingredient 

fenpyrazamine (4 lbs a.i. per gallon). There are no proposed residential uses; therefore, only 

occupational exposure is assessed in this memorandum.

Fenpyrazamine has a low order of acute toxicity and is classified as Toxicity Category III for the 

oral, dermal and inhalation routes of exposure. It produces minimal eye irritation (Toxicity 

Category IV) and is not a dermal irritant (Toxicity Category IV). It is a dermal sensitizer. 

In the dermal toxicity study there is no evidence of enhanced susceptibility of the young and all 

critical effects of concern were evaluated; a dermal hazard was not identified and therefore no 

quantification of risk is required. The short- and intermediate-term inhalation endpoints were 

derived from the developmental rabbit study in which the maternal LOAEL was 50 mg/kg/day 

based on decreased body weight and food consumption (NOAEL = 30 mg/kg/day). The 

developmental rabbit NOAEL of 30 mg/kg/day is supported by NOAELs identified in the 2-

generation reproduction study and the 90-day dog study.

Occupational handler inhalation MOEs are greater than the level of concern of 100 for all 

scenarios assessed associated with the proposed uses and are therefore not of concern. No 

quantification of dermal post-application risk is required as no dermal hazard was identified.

Based on the Agency's current practices, a quantitative non-cancer post-application inhalation 

exposure assessment is not needed for fenpyrazamine at this time. If new policies or procedures 

are put into place, the Agency may revisit the need for a quantitative post-application inhalation 

exposure assessment for fenpyrazamine.

The proposed restricted-entry interval (REI) for fenpyrazamine is 12 hours; based on the acute 

toxicity of the chemical, this REI meets the Worker Protection Standard (WPS) requirement.

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 studies from 

PHED 1.1; the AHETF database; and the ORETF database, are (1) subject to ethics review 
Page 5 of 18

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 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

2.0 Summary of Conclusions/Data Deficiencies

There are no occupational/residential risk estimates of concern associated with the proposed new 

uses of fenpyrazamine. There are no data gaps in the exposure database. As quantification of 

dermal risk is not required for fenpyrazamine, a dislodgeable foliar residue (DFR) study is not 

required for fenpyrazamine at this time. Additionally, as there are no proposed uses on turf, a 

turf transferable residue (TTR) study is not required for fenpyrazamine at this time.

3.0 Hazard Characterization

Acute Toxicity

Fenpyrazamine has a low order of acute toxicity and is classified as Toxicity Category III for the 

oral, dermal and inhalation routes of exposure. It produces minimal eye irritation (Toxicity 

Category IV) and is not a dermal irritant (Toxicity Category IV). It is a dermal sensitizer. 

Table 3.1.1. Acute Toxicity Profile – Fenpyrazamine Technical

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

870.1100 Acute oral [rat] 48400106 LD50 > 2000 

mg/kg (♀) III

870.1200 Acute dermal [rat] 48400109 LD50 > 2000 

mg/kg (♂,♀) III

870.1300 Acute inhalation [rat] 48400111 LC50 > 0.61 

mg/L (♂, ♀) III

870.2400 Acute eye irritation [rabbit] 48400112 Minimally 

irritating IV

870.2500 Acute dermal irritation [rabbit] 48400115 Not irritating IV

870.2600 Skin sensitization [Guinea pig] 48400117 Dermal 

sensitizer N/A

Toxicological PODs Used for Risk Assessment

ToxSAC memo; FENPYRAZAMINE- Summary of Toxicology Science Advisory Council (ToxSAC) Meeting of 

August 2, 2012; Jessica Kidwell; September 26, 2012.

Short- and Intermediate-Term Incidental Oral Endpoint: This endpoint was not established 

since there are no residential uses being proposed which would raise the concern for incidental 

oral exposure of children.
Page 6 of 18

Short- (1-30 days), Intermediate- (1-6 months) and Long-Term Dermal Endpoints: An 

acceptable/guideline dermal toxicity study is available. No effects were observed at the limit 

dose (1000 mg/kg/day). Since there is no evidence of enhance susceptibility of the young and all 

critical effects of concern were evaluated in the dermal study, a dermal hazard was not identified 

and therefore no quantification of risk is required.

Short- (1-30 days) and Intermediate- (1-6 months) Term Inhalation Endpoints: The short- and 

intermediate-term inhalation endpoints were derived from the developmental rabbit study in 

which the maternal LOAEL was 50 mg/kg/day based on decreased body weight and food 

consumption (NOAEL = 30 mg/kg/day). The developmental rabbit NOAEL of 30 mg/kg/day is 

supported by NOAELs identified in the 2-generation reproduction study and the 90-day dog 

study. 

Table 3.1.2. Summary of Toxicological Doses and Endpoints for Fenpyrazamine for Use in Occupational Human 

Health Risk Assessments

Exposure/ Scenario Point of 

Departure

Uncertainty 

Factors

Level of 

Concern for 

Risk Assessment

Study and Toxicological 

Effects

Dermal Short- ,Intermediate-, 

and Long-Term (1-30 days 

and 1-6 months)

No hazard identified. No quantification required.

Inhalation Short- and 

Intermediate-Term (1-30 days, 

and 1-6 months)

NOAEL = 

30 mg/kg/day

UFA= 10x 

UFH= 10x

Occupational 

LOC for MOE = 

100

Developmental Toxicity 

Study-Rabbit

LOAEL = 50 mg/kg/day 

based on decreased body 

weight and food 

consumption 

Cancer (oral, dermal, 

inhalation)

Based on the lack evidence of carcinogenicity in mice and rats, in accordance with the 

Agency's 2005 Guidelines for Cancer Risk Assessment, fenpyrazamine is classified a 

"Not Likely to be Carcinogenic to Humans". 

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

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

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a 

NOAEL. UFS = use of a short-term study for long-term risk assessment. UFDB = to account for the absence of key 

data (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.

Inhalation absorption

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

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

Body Weight

The standard body weight for the general population (80 kg) was used for all exposure scenarios 

covered in this risk assessment since the endpoints selected were not developmental and/or fetal 

effects.
Page 7 of 18

4.0 Use Profile 

Table 4.1.1. Summary of Directions for Use of Fenpyrazamine.

Applic. 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

PHI 

(days) Use Directions and Limitations

Almond

Aerial, 

Chemigation, 

Ground

Foliar Spray

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

8-12 fl 

oz (0.25-

0.375 lb 

ai/A)

2 Sequential 

Applications, 

3 

Applications 

per Season

36 fl oz 

(1.125 lb 

ai/A)

21

For Aerial Application: use a 

minimum of 20 gal of water / acre.

For Ground Application: use a 

minimum of 100 gal of water/acre.

Immediate Rotational Interval

For Brown Rot and Blossom 

Blight: Begin applications at pink 

bud (approx. 5% of bloom). If 

conditions are favorable for 

disease development, make 

additional applications at full 

bloom and at petal fall. For Green 

Fruit Rot/Jacket Rot: Begin 

applications prior to disease 

development. Generally, a single 

application at full bloom is most 

effective.

Grape (Small Fruit Vine Climbing Subgroup, Except Fuzzy Kiwifruit, 13-07F)

Aerial, 

Chemigation, 

Ground

Foliar Spray

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

12-16 fl 

oz 

(0.375-

0.5 lb 

ai/A)

2 Sequential 

Applications, 

3 

Applications 

per Season

48 fl oz (1.5 

lb ai/A) 3

For Aerial Application: use a 

minimum of 20 gal of water / acre.

For Ground Application: use a 

minimum of 100 gal of water/acre.

Immediate Rotational Interval

For Botrytis Bunch Rot: First 

application at early bloom. 

Second application at pre-bunch 

closure. Third application at 

veraison. Up to 3 days prior to 

harvest.

Lettuce (Head and Leaf)

Aerial, 

Chemigation, 

Ground

Foliar Spray

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

12-16 fl 

oz 

(0.375-

0.5 lb 

ai/A)

2 Sequential 

Applications, 

3 

Applications 

per Season

48 fl oz (1.5 

lb ai/A) 14

For Aerial Application: use a 

minimum of 5 gal of water / acre.

For Ground Application: use a 

minimum of 20 gal of water / acre.

Immediate Rotational Interval

For Lettuce Drop and Gray Mold: 

Apply from planting to just after 

thinning and again 10 days later. 

If conditions still favor disease 

development, a third application 

should be made 7-10 days after the 

second spray.
Page 8 of 18

Table 4.1.1. Summary of Directions for Use of Fenpyrazamine.

Applic. 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

PHI 

(days) Use Directions and Limitations

Strawberry (Low Growing Berry Subgroup 13-07G)

Aerial, 

Chemigation, 

Ground

Foliar Spray

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

12-16 fl 

oz 

(0.375-

0.5 lb 

ai/A)

2 Sequential 

Applications, 

4 

Applications 

per Season

64 fl oz (2 lb 

ai/A) 0

For Aerial Application: use a 

minimum of 5 gal of water / acre.

For Ground Application: use a 

minimum of 20 gal of water / acre.

Immediate Rotational Interval

For Gray Mold: First application at 

early bloom and continue on a 7 to 

14 day interval until last harvest.

Ornamentals (Greenhouse and Nursery)

Aerial, Ground, 

Chemigation, 

Handheld

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

12-16 fl 

oz/100 

gal 

(0.375-

0.5 lb 

ai/100 

gal)

2 Sequential 

Applications, 

3 

Applications 

per Growing 

Cycle

48 oz/A per 

growing 

cycle

N/A

For chemigation to ornamental 

sites apply this product only 

through microirrigation, overhead 

irrigation or motorized calibrated 

irrigation equipment.

For Botrytis Blight and Gray 

Mold: Apply before disease 

development. Reapply after 7 to 

14 days. 

100 gal of spray solution will treat 

approximately 20,000 sq ft of area. 

Apply the spray solution to all 

plant surfaces and to the point of 

run-off.

Bushberry (Subgroup 13-07B)

Aerial, 

Chemigation, 

Ground

Foliar Spray

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

12-16 fl 

oz 

(0.375-

0.5 lb 

ai/A)

2 Sequential 

Applications, 

3 

Applications 

per Season

48 fl oz (1.5 

lb ai/A) 0

For Aerial Application: use a 

minimum of 5 gal of water / acre.

For Ground Application: use a 

minimum of 20 gal of water / acre.

Immediate Rotational Interval

For Gray Mold and Mummy 

Berry: Apply when conditions 

favor disease development and 

prior to infection. Continue 

applications on a 7 to 14-day 

interval.

Caneberry (Subgroup 13-07A)

Aerial, 

Chemigation, 

Ground

Foliar Spray

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

12-16 fl 

oz 

(0.375-

0.5 lb 

ai/A)

2 Sequential 

Applications, 

3 

Applications 

per Season

48 fl oz (1.5 

lb ai/A) 0

For Aerial Application: use a 

minimum of 5 gal of water / acre.

For Ground Application: use a 

minimum of 20 gal of water / acre.

Immediate Rotational Interval

For Gray Mold: First application at 

early bloom and continue on a 7 to 

14 day interval until last harvest.
Page 9 of 18

Table 4.1.1. Summary of Directions for Use of Fenpyrazamine.

Applic. 

Timing, Type, 

and Equip.

Formulation 

[EPA Reg. 

No.]

Applic. 

Rate (lb 

ai/A)

Max. No. 

Applic. per 

Season

Max. 

Seasonal 

Applic. Rate 

(lb ai/A)

PHI 

(days) Use Directions and Limitations

Ginseng

Ground, 

Chemigation

Foliar Spray

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

12-16 fl 

oz 

(0.375-

0.5 lb 

ai/A)

2 Sequential 

Applications, 

4 

Applications 

per Season

64 fl oz (2 lb 

ai/A) 2

For Ground Application: use a 

minimum of 50 gal of water / acre.

Immediate Rotational Interval

For Gray Mold Blight: Begin 

applications when conditions favor 

disease development (cool, wet 

weather and high humidity). 

Repeat at 7- to 14- day intervals if 

favorable conditions persist.

Pistachio

Aerial, 

Chemigation, 

Ground

Foliar Spray

V-10135 4 

SC Fungicide

Suspension 

Concentrate

4 lb ai/gal

12 fl oz 

(0.375 lb 

ai/A)

2 Sequential 

Applications, 

3 

Applications 

per Season

36 fl oz 

(1.125 lb 

ai/A)

21

For Aerial Application: use a 

minimum of 20 gal of water / acre.

For Ground Application: use a 

minimum of 100 gal of water/acre.

Immediate Rotational Interval

For Blossom, Shoot and Fruit 

Blight: Begin applications at 5 to 

10% bloom. If conditions are 

favorable for disease development, 

make additional applications at full 

bloom then every 7 to 10 days or 

when conditions favor disease 

development.

5.0 Residential Exposure and Risk Estimates

There are no proposed residential uses of fenpyrazamine at this time. 

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 fenpyrazamine. 

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 information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. 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. 
Page 10 of 18

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. 

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 fenpyrazamine at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III) and low vapor pressure (2.17x10-10 mmHg at 25 oC). 

However, volatilization of pesticides may be a source of post-application inhalation exposure to 

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

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

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

March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies 

and procedures to identify the need for and, subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are developed, the Agency may revisit the need for a quantitative post-application 

inhalation exposure assessment for fenpyrazamine.

6.0 Occupational Exposure and Risk Estimates

6.1 Occupational Handler Exposure/Risk Estimates

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

application process. HED believes that there are distinct job functions or tasks related to 

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

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

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

manner specific to each application event. 

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

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

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

following scenarios: 

Mixing/Loading suspension concentrate for ground, air, and chemigation application;

Applying spray by aerial and ground equipment; 

Flagging in support of aerial application; and
Page 11 of 18

Mixing/Loading/Applying suspension concentrate for handheld equipment application.

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: 

Application rates on the labels are as follows:

The maximum single application rate for almonds and pistachio is 0.375 lb ai/acre. 

The maximum single application rate for grapes, lettuce, low growing berry subgroup, 

bushberry subgroup, caneberry subgroup, and ginseng is 0.5 lb ai/acre. 

The application rate for ornamentals grown in greenhouse and nursery is 0.5 lb ai/100 

gallons. Directions on the label indicate that for ornamental applications, 100 gallons of 

spray solution will treat approximately 20,000 ft2of area. At a rate of 0.5 lb/100 gallons, 

this equates to an approximate application rate of 1.09 lb ai/acre for ornamentals grown 

in greenhouses and nursery.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. 

Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, 

include PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force 

(ORETF) database, or other registrant-submitted occupational exposure studies. Some of these 

data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. 

The standard values recommended for use in predicting handler exposure that are used in this 

assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit 

Exposure Surrogate Reference Table” (http://www.epa.gov/opp00001/science/handler-exposuretable.pdf), which, along with additional information on HED policy on use of surrogate data, 

including descriptions of the various sources, can be found at 

http://www.epa.gov/pesticides/science/handler-exposure-data.html.

Estimates of inhalation exposure were calculated. 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 product label directs mixers, loaders, applicators and 

other handlers to wear long-sleeved shirt and long pants, chemical-resistant gloves, socks and 

shoes.

Area Treated or Amount Handled: 

Area treated or amount handled includes:

Aerial equipment: 350 acres for field and orchard crops, 60 acres for nursery crops

Airblast: 40 acres for orchard crops, 20 acres for nursery crops

Chemigation: 350 acres for orchard and field crops, 60 acres for nursery and greenhouse 

crops

Groundboom equipment: 80 acres for field crops, 60 acres for nursery and greenhouse 

crops, and 40 acres for field-grown ornamentals
Page 12 of 18

Flagger: 350 acres for orchard and field crops, 60 acres for nursery crops

Body Weight: 

The standard body weight for the general population (80 kg) was used for all exposure scenarios 

covered in this risk assessment since the endpoints selected were not developmental and/or fetal 

effects.

 

Absorption factors: 

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

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

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 fenpyrazamine, based on the proposed use, short-and intermediate-term exposures are

anticipated for the following reasons: (1) 3 to 4 applications of the fungicide can be made to 

crops per season, and (2) commercial applicators could apply and re-apply the fungicide to 

multiple crops over a period of weeks (e.g., completing multiple applications for multiple clients 

for multiple crops within a region). 

Mitigation/Personal Protective Equipment: Occupational handler exposure assessments are 

completed by HED using different levels of risk mitigation. Typically, HED uses a tiered 

approach. The lowest tier is designed as the baseline exposure scenario (i.e., long-sleeve shirt, 

long pants, shoes, socks, no respirator). If risk estimates are of concern at baseline attire, then 

increasing levels of PPE (i.e., gloves, respirators) are evaluated. If risk estimates remain a 

concern with maximum PPE, then engineering controls (i.e., enclosed cabs or cockpits, watersoluble packaging, and closed mixing/loading systems) are evaluated. This approach is used to 

ensure that the lowest level of risk mitigation that provides adequate protection is selected, since 

the addition of PPE and engineering controls involves an additional expense to the user and (in 

the case of PPE) also involves an additional burden to the user due to decreased comfort and 

dexterity and increased heat stress and respiratory stress.

Occupational Handler Non-Cancer Exposure and Risk Estimate Equations

Potential daily exposures for occupational handlers were calculated using the following 

formulas:

Daily Exposure (mg ai /day) = UE (μg ai / lb ai) * AR (lb ai /A) * AT (A /day) * 1E-3 mg/μg

where:
Page 13 of 18

Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption,

UE = Unit Exposure (μg ai / lb ai),

AR = maximum application rate according to proposed label (lb ai /A), and

AT = daily acres treated (A /day).

The daily doses were calculated using the following formula:

Average Daily Dose (mg ai/kg/day) = [Daily Exposure (mg ai/day) * Absorption (%)]

Body Weight (kg)

where:

Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg 

pesticide active ingredient/kg body weight/day),

Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption,

Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as 

the skin and lungs (%), and

Body Weight = Body weight determined to represent the population of interest in a risk 

assessment (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 were compared to the appropriate POD (i.e. NOAEL) to assess the risk to occupational 

handlers for each exposure route. All MOE values were calculated using the following formula:

MOE = POD (typically a NOAEL in mg/kg/day) 

ADD (mg/kg/day)

where:

MOE = Margin of Exposure: value used by HED to represent risk or risk estimates (unitless),

POD = Point of Departure,

NOAEL = No Observed Adverse Effect Level (mg/kg/day): Dose level in a toxicity study, where no 

observed adverse effects occurred in the study, and

ADD = Average Daily Dose (mg/kg/day): the absorbed dose received from exposure to a 

pesticide in a given scenario.

Combining Exposures/Risk Estimates:

Dermal and inhalation risk estimates were not combined in this assessment, since no dermal 

hazard was identified; therefore no dermal quantitative risk assessment is required. 

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

Occupational handler inhalation risk estimates are not of concern (MOEs > LOC) for all 

proposed uses assessed. The label-required PPE on the proposed label is that all handlers must 

wear long-sleeved shirt and long pants, chemical-resistant gloves, and socks and shoes. 

Inhalation MOEs range from 4,000 (mixing/loading/applying soluble concentrate formulation by 

mechanically-pressurized handwand) to 550,000 (mixing/loading soluble concentrate in support 

of airblast application). A summary of inhalation risk estimates for occupational handlers can be 

found in Table 6.1.1.
Page 14 of 18

The Agency has evaluated scenarios that may be limited in nature such as flagging during aerial 

applications because engineering controls (i.e., Global Positioning Satellite technology) are now 

predominantly used as indicated by the 1998 National Agricultural Aviation Association 

(NAAA) survey of their membership. It appears, however, flaggers are still used in 

approximately 10 to 15 percent of aerial application operations. In cases like these, the Agency 

strongly encourages the use of the engineering control system but will continue to evaluate risks 

for flaggers and any other population where a clear exposure pathway exists until the potential 

for exposure is eliminated. The Agency is aware that NAAA is conducting another survey on 

exposure issues and will consider those results as are timely and appropriate.

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); pilots are not required to wear protective gloves. With this level of protection, there 

are no risk estimates of concern for applicators.
Page 15 of 18

Table 6.1.1. Short-/Intermediate-Term Occupational Exposure and Risk Estimates for Fenpyrazamine. 

Exposure Scenario Crop or Target

Inhalation Unit 

Exposure (ug/lb ai)1

Maximum

Application Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation

Baseline Dose (mg/kg/day)4 MOE5

Mixer/Loader

M/L, L/SC/EC, Aerial, Broadcast

Nursery

0.219

1.09 lb ai/acre 60 acres 0.000179 170,000

Orchard, Field Crop 0.5 lb ai/acre 350 acres 0.000479 63,000

M/L, L/SC/EC, Airblast, 

Broadcast

Nursery 1.09 lb ai/acre 20 acres 0.0000596 500,000

Orchard 0.5 lb ai/acre 40 acres 0.0000548 550,000

M/L, L/SC/EC, Chemigation, 

Broadcast

Orchard, Field Crop 0.5 lb ai/acre 350 acres 0.00479 63,000

Greenhouse, Nursery 1.09 lb ai/acre 60 acres 0.000179 170,000

M/L, L/SC/EC, Groundboom, 

Broadcast

Field-grown ornamentals 1.09 lb ai/acre 40 acres 0.000119 250,000

Nursery, Greenhouse 1.09 lb ai/acre 60 acres 0.000179 170,000

Field Crop 0.5 lb ai/acre 80 acres 0.00011 270,000

Applicator

Applicator, Spray, Aerial, 

Broadcast

Nursery Engineering Control:

0.068

1.09 lb ai/acre 60 acres 0.0000556 540,000

Orchard, Field Crop 0.5 lb ai/acre 350 acres 0.000149 200,000

Applicator, Spray, Airblast, 

Broadcast

Nursery

4.71

1.09 lb ai/acre 20 acres 0.00129 23,000

Orchard 0.5 lb ai/acre 40 acres 0.00118 25,000

Applicator, Spray, Groundboom, 

Broadcast

Field-grown ornamentals

0.34

1.09 lb ai/acre 40 acres 0.000185 160,000

Nursery, Greenhouse 1.09 lb ai/acre 60 acres 0.000278 110,000

Field Crop 0.5 lb ai/acre 80 acres 0.00017 180,000

Flagger

Flagger, Spray, Aerial, Broadcast

Nursery

0.35

1.09 lb ai/acre 60 acres 0.000286 100,000

Orchard, Field Crop 0.5 lb ai/acre 350 acres 0.000766 39,000

Mixer/Loader/Applicator

M/L/A, L/SC/EC, Backpack, 

Broadcast Greenhouse, Nursery 140

0.005 lb ai/gallon

40 gallons 0.00035 86,000

M/L/A, L/SC/EC, Manuallypressurized handwand, Broadcast Greenhouse, Nursery 30 40 gallons 0.000075 400,000

M/L/A, L/SC/EC, Mechanicallypressurized handwand, Broadcast

Nursery 3.9 1000 

gallons

0.000244 120,000

Greenhouse 120 0.0075 4,000
Page 16 of 18

M/L = Mixer/Loader. M/L/A = Mixer/Loader/Applicator. L/SC/EC = Liquid/Suspension Concentrate/Emulsifiable Concentrate

1 Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012); includes data from PHED/ORETF/AHETF (level of mitigation: Baseline, no respirator).

2 Based on proposed label. The maximum single application rate for almonds and pistachios is 0.375 lb ai/A; however this use is covered by the assessed maximum application rate of 0.5 lb ai/A for 

other orchard crops.

3 Exposure Science Advisory Council Policy #9.1.

4

Inhalation Dose = Inhalation Unit Exposure (ug/lb ai) x Conversion Factor (0.001 mg/ug) x Application Rate (lb ai/acre or gal) x Area Treated or Amount Handled Daily (A or gal/day) /BW (80 kg).

5

Inhalation MOE = Inhalation NOAEL (30 mg/kg/day)/ Inhalation Dose (mg/kg/day).
Page 17 of 18

6.2 Occupational Post-application Exposure/Risk Estimates

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

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

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

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

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

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

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

no dermal hazard has been identified for fenpyrazamine, quantification of dermal postapplication risk is not required. Further, a post-application inhalation exposure assessment was 

not performed at this time.

6.2.1 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 fenpyrazamine at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category III) and the low vapor pressure (2.17x10-10 mmHg at 25 

oC). However, there are multiple potential sources of post-application inhalation exposure to 

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

sources include volatilization of pesticides and resuspension of dusts and/or particulates that 

contain pesticides. The Agency sought expert advice and input on issues related to volatilization 

of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory 

Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the 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 fenpyrazamine.

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.

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting 

workers from inhalation exposures during and after greenhouse applications through the use of 

ventilation requirements [40 CFR 170.110, (3) (Restrictions associated with pesticide 

applications)].
Page 18 of 18

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

As no dermal hazard has been identified for fenpyrazamine, quantification of dermal postapplication risk is not required. In accordance with the updated 40 CFR Part 158 data 

requirements (2007), one or more dislodgeable foliar residue (DFR) studies are required when a 

pesticide has residential or occupational uses that could result in postapplication dermal 

exposure. However, as quantification of dermal risk is not required for fenpyrazamine, a DFR 

study is not required for fenpyrazamine at this time. Additionally, a turf transferable residue 

(TTR) study is required for all occupational (e.g., sod farms, golf courses, parks, and recreational 

areas) or residential turf uses. As there are no proposed uses on turf, a TTR study is not required 

for fenpyrazamine at this time.

Restricted Entry Interval

The REI specified on the proposed label is based on the acute toxicity of fenpyrazamine. 

Fenpyrazamine is classified as Toxicity Category III via the dermal route, Toxicity Category IV 

for acute eye irritation, and Toxicity Category IV for acute dermal irritation. It is a skin 

sensitizer. Under WPS for agricultural pesticides, ai’s classified as Acute III or IV for acute 

dermal, eye irritation and primary skin irrigation are assigned a 12-hour REI. Therefore, the 

WPS interim REI of 12 hours is adequate to protect agricultural workers from post-application 

exposures to fenpyrazamine.