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health risk resulting from the proposed and registered uses of trifloxystrobin are provided in this 

document. The residue chemistry review and dietary risk assessment were conducted by 

Meheret Negussie; the aggregate risk assessment was conducted by Nancy Keller.
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Table of Contents

1.0 Executive Summary..............................................................................................................5

2.0 HED Recommendations.......................................................................................................7

2.1 Data Deficiencies ............................................................................................................ 7

2.2 Tolerance Considerations.............................................................................................. 7

2.2.1 Enforcement Analytical Method................................................................................... 7

2.2.3 Revisions to Petitioned-For Tolerances........................................................................ 8

2.2.4 International Harmonization ........................................................................................ 8

3.0 Introduction...........................................................................................................................9

3.1 Chemical Identity ........................................................................................................... 9

3.2 Physical/Chemical Characteristics ............................................................................. 10

3.3 Pesticide Use Pattern.................................................................................................... 10

3.4 Anticipated Exposure Pathways................................................................................. 11

3.5 Consideration of Environmental Justice.................................................................... 11

4.0 Hazard Characterization and Dose-Response Assessment.............................................12

4.1 Toxicology Studies Available for Analysis................................................................. 12

4.2 Absorption, Distribution, Metabolism and Excretion (ADME) .............................. 12

4.3 Toxicological Effects .................................................................................................... 13

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 14

4.4.1 Completeness of the Toxicology Database.......................................................... 14

4.4.2 Evidence of Neurotoxicity .................................................................................... 14

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal .... 14

4.4.4 Residual Uncertainty in the Exposure Database................................................ 14

4.5 Recommendation for Combining Routes of Exposure for Risk Assessment.......... 14

4.6 Cancer Classification and Risk Assessment Recommendation ........................ 15

4.7 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment........................................................................................................................... 15

5.0 Dietary Exposure and Risk Assessment............................................................................16

5.1 Residues of Concern Summary and Rationale.......................................................... 16

5.2 Food Residue Profile .................................................................................................... 17

5.3 Water Residue Profile.................................................................................................. 17

5.4 Dietary Risk Assessment.............................................................................................. 18

5.4.1 Description of Residue Data Used in Dietary Assessment ................................ 18

5.4.2 Acute Dietary Risk Assessment ........................................................................... 19

5.4.3 Chronic Dietary Risk Assessment ....................................................................... 19

5.4.4 Cancer Dietary Risk Assessment......................................................................... 19

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................................20

6.1 Combined Residential Risk Estimates........................................................................ 20

6.2 Recommendations for Aggregate Assessment........................................................... 21

6.3 Residential Bystander Post-Application Inhalation Exposure ................................ 21

6.4 Non-Occupational Spray Drift Exposure and Risk Estimates................................. 21

7.0 Aggregate Exposure/Risk Characterization.....................................................................22

7.1 Acute Aggregate Risk................................................................................................... 22

7.2 Short-Term Aggregate Risk........................................................................................ 22

7.3 Intermediate-Term Aggregate Risk ........................................................................... 23
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7.4 Chronic Aggregate Risk .............................................................................................. 23

7.5 Cancer Aggregate Risk ................................................................................................ 23

8.0 Cumulative Exposure/Risk Characterization ..................................................................23

9.0 Occupational Exposure/Risk Characterization ...............................................................24

10.0 References............................................................................................................................24

Appendix A. Toxicology Profile and Executive Summaries...................................................26

A.1 Toxicology Data Requirements................................................................................... 26

A.2 Toxicity Profile of Trifloxystrobin Technical............................................................ 27

Appendix B. Physical/Chemical Properties.............................................................................30

Appendix C. Review of Human Research ................................................................................30

Appendix D. Residential Exposure/Risk Summary Table......................................................31
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1.0 Executive Summary

Trifloxystrobin is a strobilurin-class broad-spectrum fungicide that controls foliar, soilborne, and 

seedling fungal diseases in various agricultural crops. It works by interrupting mitochondrial 

respiration in plant-pathogenic fungi, thus inhibiting spore germination and mycelial growth.

In PP#4F8288, Bayer CropScience (Bayer) has submitted a petition for trifloxystrobin to 

establish tolerances on leafy greens (crop subgroup 4A), head and stem Brassica vegetables 

(crop subgroup 5A), leafy Brassica greens (crop subgroup 5B), herbs (crop group 19A), and 

spices, except black pepper (crop subgroup 19B); and, to amend the current tolerance on leafy 

petioles (crop subgroup 4B). In addition, Bayer is proposing to convert the potato tolerance to 

the tuberous and corm vegetables subgroup (crop subgroup 1C), the grape tolerance to the small 

fruit vine climbing (subgroup 13-07F), and the strawberry tolerance to the low growing berries 

(subgroup 13-07G), based on the currently approved potato, grape, and strawberry uses for this 

active ingredient, respectively. All of these uses are proposed to be added to the end use product 

label for Gem® 500 SC (EPA Reg. No. 264-826), a suspension concentrate (SC) formulation 

containing 42.6% active ingredient (ai) by weight (4.05 lb ai/gal).

Since the last risk assessment, there have been no changes to the hazard characterization or 

hazard profile of trifloxystrobin (DP413109, N. Tsaur, 06/03/2014). 

Proposed Use Profile

Gem 500 SC may be applied as a foliar spray via groundboom, aircraft, chemigation, and 

handheld equipment. Human flagging is also allowed on the label. The proposed maximum 

single application rate for all proposed crops, is 3.8 fl oz product per acre (0.12 lb ai/acre, or 

0.012 lb ai/gallon). Annual applications are limited to two per year and may be repeated on a 5-

to 10-day interval, up to a maximal seasonal application rate of 0.24 lb ai/acre/year.

Exposure Profile

Exposure pathways include dietary (food and drinking water), non-occupational (residential) and 

occupational exposure sources for the proposed and existing registered uses of trifloxystrobin. 

Exposures via diet and drinking water are expected for all durations; residential handler and postapplication exposures are only expected for the short-term duration; and occupational handler 

and post-application exposures are expected for short- and intermediate-term durations. The 

proposed label requires occupational handlers to wear long pants, long sleeves, shoes, socks, and 

chemical-resistant gloves.

Toxicity/Hazard

The toxicology database for trifloxystrobin is complete and adequate for risk assessment. The 

primary target organ of toxicity in subchronic and chronic studies in dogs, mice, and rats is the 

liver. The effects of reduced body weight and food consumption were also found in the majority 

of the toxicity studies. There are no susceptibility concerns regarding developmental or

reproductive toxicity, and no evidence of neurotoxicity or immunotoxicity in the trifloxystrobin 

toxicology database. Trifloxystrobin exhibits low acute mammalian toxicity via oral (Toxicity 

Category IV), dermal (Toxicity Category IV), and inhalation (Toxicity Category IV) routes of 

exposure. Trifloxystrobin is a mild eye and skin irritant, and is a strong dermal sensitizer. 
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Trifloxystrobin is classified as “Not likely to be Carcinogenic to Humans” based on the lack of 

evidence of carcinogenicity in mice and rats. Trifloxystrobin is not mutagenic in vivo and in 

vitro. The level of concern (LOC) for all routes and durations of exposure is 100.

Dietary Exposure (Food and Water) and Risk Estimates

The acute and chronic dietary exposure and risk estimates were not of concern. They were 

highly conservative since they assumed tolerance level residues, anticipated residues for some 

crops, 100% crop treated (CT), and included mainly default processing factors. There were no 

appropriate toxicological effects attributable to a single exposure (dose) for the general 

population; therefore, a dose and endpoint were not identified. An acute endpoint was identified 

for females 13-49 years old. Acute and chronic dietary exposure and risk estimates are below 

HED’s LOC for the U.S. population and all population subgroups. The acute dietary (food +

drinking water) risk estimate for females 13-49 years old is 3.1% of the acute population 

adjusted dose (aPAD) at the 95th percentile. The chronic dietary (food + drinking water) risk 

estimates represented 34% of the chronic population adjusted dose (cPAD) for the general U.S. 

population and 71% of the cPAD for all infants <1 year old, the most highly exposed population 

subgroup.

Residential Exposure and Risk Estimates

Although there are no residential exposures associated with the proposed uses, all existing 

residential exposures were previously assessed according to HED’s 2012 Residential Standard 

Operating Procedures (SOPs) and to incorporate previous changes to the dermal risk assessment 

point of departure and changes in the policy for body weight assumptions. There are no 

registered products that would result in residential handler or post-application risk estimates of 

concern. Short-term residential handler inhalation margins of exposure (MOEs) for the existing 

uses of trifloxystrobin range from 8,100 to 170,000,000. Short-term post-application incidental 

oral MOEs for all residential scenarios range from 730 to 330,000.

Aggregate Exposure Risk Estimates

There is only potential for short-term aggregate exposure to trifloxystrobin via the dietary and 

residential pathways; residential exposures include inhalation (adults) and incidental oral 

(children 1 to <2 years). For adults and children 1 to <2 years old, the short-term aggregate risk 

estimates are not of concern; the MOEs are 290 and 130 respectively.

Occupational Handler and Post-Application Exposures and Risk Estimates

Although there are occupational exposures associated with all of the proposed uses, existing 

occupational risk assessments are protective of the proposed uses, and a new occupational risk 

assessment was not conducted for this action. The 12-hour restricted entry interval (REI) listed 

on the label is adequate to protect agricultural workers from post-application exposures to 

trifloxystrobin.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income 

Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf).
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2.0 HED Recommendations

HED has examined the toxicology and residue chemistry databases for trifloxystrobin. Pending 

submission of a revised Section F (tolerances), there are no issues that would preclude granting 

registration for the requested uses of trifloxystrobin, or establishment of the recommended 

tolerance for combined residues of trifloxystrobin and its metabolite CGA-321113 (see Table 

2.2.2). The specific tolerance recommendations are discussed in Section 2.2.

2.1 Data Deficiencies

Guideline 875.2100 – Turf Transferable Residues (TTR) Study

At this time, EPA is requiring the 40 CFR TTR data because the estimated residential turf postapplication exposure, using default TTR values for trifloxystrobin, is not minimal in comparison 

to the level of concern (i.e. the calculated MOE is not greater than 10 times higher than the level 

of concern; MOE = 730 compared to the LOC of 100).

2.2 Tolerance Considerations

Tolerances are currently established for the combined residues of trifloxystrobin and the free 

form of its acid metabolite CGA–321113 in/on various crop and livestock commodities ranging 

from 0.01 ppm to 38 ppm [40 CFR §180.555(a)]. 

2.2.1 Enforcement Analytical Method

An adequate gas chromatography method with nitrogen phosphorus detection (GC/NPD), 

Method AG-659A, is available for enforcing tolerances for the combined residues of 

trifloxystrobin and CGA-321113 in plant and livestock commodities. Samples from the 

submitted crop field trials on chickpea and dry peas (seed, forage, and hay) were analyzed for 

residues of trifloxystrobin and CGA-321113 using a high performance liquid chromatography 

method with tandem mass spectrometry detection (LC/MS/MS). Residues of CGA-321113 were 

converted to parent equivalents using a molecular weight conversion factor. The method was 

adequately validated in conjunction with the analysis of crop field trial samples. The lowest 

level of method validation (LLMV) is equivalent to the limit of quantitation (LOQ) which was 

0.010 ppm for each analyte in/on all matrices.

2.2.2 Recommended Tolerances

A revised Section F needs to be submitted to reflect the correct commodity definitions as shown 

below in Table 2.2.2.

Table 2.2.2. Tolerance Summary for Trifloxystrobin

Commodity Tolerance (ppm) Comments

Proposed Recommended Correct Commodity Definition

40 CFR §180.555(a)(1)

Leafy greens, subgroup 4A 30 30 Leafy greens subgroup 4A
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Table 2.2.2. Tolerance Summary for Trifloxystrobin

Commodity Tolerance (ppm) Comments

Proposed Recommended Correct Commodity Definition

Leafy petioles, subgroup 

4B1

9 9 Leaf petioles subgroup 4B

Head and stem brassica 

subgroup 5A

2 2 Brassica, head and stem, subgroup 

5A

Leafy brassica Subgroup 

5B

30 30 Brassica, leafy greens, subgroup 

5B

Herb, subgroup 19A 200 200 Herb subgroup 19A

Spice, subgroup 19B, 

except black pepper

30 30 Dill, seed

Tuberous and corm 

vegetable subgroup 1C

0.04 0.04 Vegetable, tuberous and corm, 

subgroup 1C

Small fruit vine climbing 

subgroup (except fuzzy 

kiwifruit), subgroup 13-

07F2

2.0 2.0 Fruit, small vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F 

Low growing berry, 

subgroup 13-07G3

1.5 1.5 Berry, low growing, subgroup 13-

07G 1 A tolerance of 3.5ppm currently exists for leafy petioles subgroup 4B. This petition is changing the use pattern 

from a 14-day pre-harvest interval (PHI) to a 0-day PHI. 2 The current tolerance on grape (the representative commodity for the subgroup) is being expanded to cover the 

entire subgroup.

3 The current tolerance on strawberry (the representative commodity for the subgroup) is being expanded to cover 

the entire subgroup and raised from the existing 1.1 ppm to 1.5 ppm.

2.2.3 Revisions to Petitioned-For Tolerances

Although HED’s recommended tolerances do not differ from the registrant’s proposed 

tolerances, a revised Section F needs to be submitted to reflect the correct commodity 

definitions.

Specifically, the Agency is revising the commodity definitions for the requested tolerances to 

reflect the common commodity vocabulary currently used by the Agency. Specifically, Head 

and stem brassica subgroup 5A was changed to Brassica, head and stem, subgroup 5A; Leafy 

brassica Subgroup 5B was changed to Brassica, leafy greens, subgroup 5B; Tuberous and corm 

vegetable subgroup 1C was changed to Vegetable, tuberous and corm, subgroup 1C; Small fruit 

vine climbing subgroup (except fuzzy kiwifruit), subgroup 13-07F was changed to Fruit, small 

vine climbing, except fuzzy kiwifruit, subgroup 13-07F; and Low growing berry, subgroup 13-

07G was changed to Berry, low growing, subgroup 13-07G. Bayer requested a tolerance for 

spice (Crop Subgroup 19B), except black pepper. Because black pepper serves as a

representative commodity for Spice, subgroup 19B, it may not be excepted from a tolerance (see 

40 CFR 180.40(h)). Without sufficient data to establish the subgroup tolerance, the Agency is 

establishing an individual tolerance for the crop for which data was submitted – dill, seed.

2.2.4 International Harmonization
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Codex maximum residue limits (MRLs) have been established for residues of trifloxystrobin 

in/on a number of commodities associated with this petition. Codex MRLs are expressed in 

terms of trifloxystrobin (parent only) while U.S. tolerances are based on the combined residues 

of trifloxystrobin and its acid metabolite CGA-321113, expressed in parent equivalents. 

Therefore, harmonization is not possible as the Codex MRLs are likely to be too low based on 

the U.S. residue definition for tolerance enforcement. 

Canadian MRLs are based on the combined residues of trifloxystrobin and its acid metabolite 

expressed as parent equivalents, and are therefore harmonized with the U.S. enforcement residue 

definition. The Canadian MRLs are consistent with the established tolerances for potato and 

grape and, therefore, will be consistent with the proposed U.S. tolerances for the tuberous and 

corm vegetables subgroup and the small vine climbing fruit, except fuzzy kiwifruit, subgroup. 

Tolerances will not be harmonized for leafy petioles subgroup 4B as the change in pre-harvest 

interval (PHI) and subsequent increase in tolerance to 9 ppm will no longer be the same as the 

Canadian MRL of 3.5 ppm. Similarly, the proposed increase in the tolerance for strawberries to 

1.5 ppm (and subsequent expansion to subgroup 13-07G) will no longer be harmonized with the 

Canadian MRL of 1.1 ppm.

Table 2.2.4 is a summary of the recommended tolerances and a comparison to Codex MRLs.

Table 2.2.4. US Recommended Tolerance/Codex MRL Comparison

United States Codex 

US Crop Subgroup Recommended 

Tolerance, ppm Commodity MRL, ppm

Leafy greens subgroup 4A 30 Lettuce, Head 15

Leaf petioles subgroup 4B 9 Celery 1

Brassica, head and stem, subgroup 5A 2 Brussels Sprouts 0.1

Flowerhead brassicas (includes 

Broccoli: Broccoli, Chinese 

and Cauliflower)

0.5

Cabbages 0.5

Brassica, leafy greens, subgroup 5B 30 None None

Herb subgroup 19A 200 None None

Dill, seed 30 None None

Vegetable, tuberous and corm, subgroup 

1C

0.04 Potato 0.2

Fruit, small fruit vine climbing, except 

fuzzy kiwifruit, subgroup 13-07F

2.0 Grape 3

Berry, low growing, subgroup 13-07G 1.5 Strawberry 1

3.0 Introduction

Trifloxystrobin is a broad-spectrum preventative fungicide used for control of many plant 

diseases in various fruit, nut, vegetable, and field crops. It is a strobilurin-class fungicide that 

controls foliar, soilborne, and seedling fungal diseases. It works by interrupting mitochondrial 

respiration in plant-pathogenic fungi, thus inhibiting spore germination and mycelial growth.

3.1 Chemical Identity
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Table 3.1. Trifloxystrobin Nomenclature

Compound

Common name trifloxystrobin

Company experimental name BO17211 or CGA-279202

IUPAC name methyl (E)-methoxyimino-{(E)-α-[1-(α,α,α,-trifluoro-m-tolyl)

ethylideneaminooxy]-o-tolyl}acetate

CAS name methyl (αE)-α-(methoxyimino)-2-[[[[(1E)-1-[3-(trifluoromethyl)phenyl]

ethylidene]amino]oxy]methyl]benzeneacetate

CAS registry number 141517-21-7

End-use product (EP) Gem® 500 SC Fungicide; 4.05 lb ai trifloxystrobin/gal; EPA Reg. No. 264-826

Compound

(metabolite CGA-321113)

Common name trifloxystrobin acid

Company experimental name CGA-321113

CAS name (α E)- α –(methoxyimino-[2-[[[(E)-1-[3-(trifluoromethyl)phenyl]ethylidene]

amino]oxy]methyl]benzeneacetic acid

CAS registry number 252913-85-2

3.2 Physical/Chemical Characteristics

Trifloxystrobin has a low vapor pressure (2.55×10-7 mm Hg at 25°C); therefore, inhalation due to

chemical vaporization is unlikely. Trifloxystrobin has a log octanol/water partition coefficient 

(log Pow) of 4.5 and is considered soluble in fat. Additionally, trifloxystrobin has a molecular 

weight of 408.4 g/mol; therefore, the potential to cross biological barriers, such as the skin, is 

somewhat limited. More detailed physicochemical properties of trifloxystrobin are summarized 

in Appendix B.

3.3 Pesticide Use Pattern

Bayer has submitted an amended label for Gem® 500 SC (EPA Reg. No. 264-826). The newly 

proposed use pattern is presented in Table 3.3.

O

N

CF3

N

O

O

CH3

O

H3C

CH3

O

N

CF3

N

OH

O O

H3C

CH3
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Table 3.3. Summary of Proposed Use Directions for Gem® 500 SC Fungicide (EPA Reg. No. 264-826)

a

Application 

Timing, Type, 

and Equipment

Single 

Maximum 

Application 

Rate

Maximum 

Number of 

Applications 

per Year

Maximum 

Annual 

Application 

Rate

PHIb

Use Directions and Limitations

days

Leafy Greens (Crop Subgroup 4A), Head and Stem Brassica Vegetables (Crop Subgroup 5A), Leafy 

Brassica Greens (Crop Subgroup 5B), Herbs (Crop Group 19A), and Spices, Except Black Pepper (Crop 

Subgroup 19B), Potato and Tuberous and Corm Vegetables Subgroup (Crop Subgroup 1C)

Broadcast 

Foliar: 

ground, aerial, 

chemigation, or 

handheld

3.8 fl oz

product/A

0.12 lb ai/A

0.012 lb 

ai/galc

2

7.6 fl oz 

product/A

0.24 lb ai/A

5-10

Do not apply more than 2 applications per 

year. Do not exceed 0.24 lb trifloxystrobin 

per acre per year. The application may be 

made by ground, chemigation, or aerial 

spray equipment. Do not apply within 30 

days of harvest. For ground equipment, a 

minimum of 10 GPA is recommended. 

For aerial equipment, a minimum of 5 

GPA is recommended.

a SC = suspension concentrate.

b PHI = pre-harvest interval.

c The application rate is based on use direction of “a minimum of 10 gallons per acre” recommended for ground 

equipment.

3.4 Anticipated Exposure Pathways

Humans may be exposed to trifloxystrobin via food and drinking water because trifloxystrobin

may be applied directly to growing crops, and application may result in trifloxystrobin reaching 

surface and ground sources of drinking water. In residential settings, adults and children may be 

exposed during handler and post-application activities. In occupational settings, applicators may 

be exposed while handling the pesticide prior to application, as well as during application. There 

is also a potential for post-application exposure for workers re-entering treated fields.

Several risk assessments have been previously prepared for the existing uses of trifloxystrobin. 

This risk assessment considers all of the aforementioned exposure pathways based on the 

proposed new use of trifloxystrobin, but also considers the existing uses as well, particularly for 

the dietary and residential exposure assessment.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf). As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the USDA under the National 

Health and Nutrition Examination Survey/What We Eat in America (NHANES/WWEIA), and 

are used in pesticide risk assessments for all registered food uses of a pesticide. These data are 
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analyzed and categorized by subgroups based on age and ethnic group. Additionally, OPP is 

able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are 

performed when conditions or circumstances warrant. Whenever appropriate, non-dietary 

exposures based on home use of pesticide products and associated risks for adult applicators and 

for toddlers, youths, and adults entering or playing on treated areas post-application are 

evaluated. Further considerations are currently in development as OPP has committed resources 

and expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Trifloxystrobin controls fungal diseases by interrupting mitochondrial respiration in plantpathogenic fungi, thus inhibiting spore germination and mycelial growth. There are no 

mammalian molecular data to specifically show this mode of action in the test animals.

4.1 Toxicology Studies Available for Analysis

The toxicology database of trifloxystrobin provides sufficient information for selecting toxicity 

endpoints and points of departure for risk assessment. The available toxicology studies include 

(1) subchronic oral toxicity studies in rats, mice, and dogs; (2) a 28-day dermal toxicity study in 

rats; (3) developmental toxicity studies in rats and rabbits; (4) a 2-generation reproduction study 

in rats; (5) chronic toxicity studies in rats and dogs; (6) carcinogenicity studies in rats and mice; 

(7) a battery of the required genotoxicity studies; (8) immunotoxicity study in rats; and (9)

metabolism studies in rats. At this time, neither a subchronic neurotoxicity study (TXR0056150, 

D. Smegal, 01/05/2012) nor a subchronic inhalation toxicity study (TXR0056957, U. Habiba, 

05/22/2014) are required.

4.2 Absorption, Distribution, Metabolism and Excretion (ADME)

With low dose oral administration of trifloxystrobin to rats, approximately 56% and 65% of the 

administered dose was absorbed, with 41% and 47% found in the bile of male and female rats, 

respectively. With high dose administration, the absorption was 41% and 27%, with 35% and 

19% in was found in the bile of male and female rats, respectively. The percentage of absorption 

was similar with either single dose administration or repeated dosing in both sexes. The time to 

peak blood concentration was 12-24 hours. The blood, liver, and kidneys were found to have the 

highest residues. Most of the examined tissues had somewhat higher residue levels in the 

females than in the males (by up to two-fold). A majority of the administered dose was 

eliminated in the feces. Less than 0.1% of the administered dose was found in the expired air. 

The total tissue and carcass contained 0.3-0.5% of the administered dose indicating essentially 

no tissue accumulation. The parent compound was extensively metabolized to approximately 35 

metabolites.

Dermal Absorption

Dermal absorption studies are not available for trifloxystrobin. In the past (TXR 0050612, S.

Dapson, 04/01/2002), the lowest observed adverse effect level (LOAEL) of 337 mg/kg/day 
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observed in the oral 28-day range-finding feeding study in rats (MRID 44496643) was compared 

to the LOAEL of 1000 mg/kg/day observed in the 28-day dermal toxicity study in rats (MRID 

44496704) to yield a calculated dermal absorption factor (DAF) of approximately 33%. Both of 

the LOAELs were based on increases in liver weight; however, when the dermal subchronic 

study was reevaluated with current criteria, the increased liver weights were not considered to be 

adverse because they were minimal and not confirmed by histopathological correlates. 

Therefore, the no observed adverse effect level (NOAEL) for this dermal subchronic study was 

set at 1000 mg/kg/day and the LOAEL was not established.

Dermal penetration study data for other strobilurins such as azoxystrobin, fluoxastrobin and 

pyraclostrobin suggest that dermal absorption of trifloxystrobin is expected to be less than 20%. 

As mentioned above, the 28-day dermal toxicity study showed no adverse dermal or systemic 

effects at dose levels (up to the limit dose of 1000 mg/kg bw/day) where toxicity was seen in 

comparable oral studies, supporting the expectation that dermal absorption is low.

4.3 Toxicological Effects

With repeated dosing, the liver is consistently the target organ for trifloxystrobin. Liver effects 

characterized by an increase in liver weights and an increased incidence of hepatocellular 

hypertrophy and/or hepatocellular necrosis were seen in rats, mice, and dogs. The effects of 

reduced body weights and food consumption were also found in the majority of the toxicity 

studies. Intestinal disturbances, as indicated by diarrhea and vomiting, were seen in dogs and 

rats at higher dose levels relative to those which caused liver and body weight effects. This 

finding was consistent with those produced by other members of the strobilurin class.

In the rabbit developmental toxicity study, an increase in the incidence of fused sternabrae was 

seen at a dose 10 times higher than the maternal LOAEL. In the rat reproduction study, both 

parents and offspring showed decreases in body weight during lactation. The rat and rabbit 

developmental and the rat reproduction toxicity data do not demonstrate an increase in 

susceptibility in the fetus or other offspring.

Trifloxystrobin was determined not to be carcinogenic in mice or rats following long-term 

dietary administration. However, it is positive for mutagenicity in Chinese Hamster V79 cells at 

cytotoxic dose levels while testing negative in the remaining mutagenicity studies.

Trifloxystrobin was not neurotoxic in the acute neurotoxicity study, nor in any of the repeated 

dose studies in the available data. The requirement for a subchronic neurotoxicity study was 

waived (TXR0056150, D. Smegal, 01/05/2014) because there is no evidence of neurotoxicity in 

the existing trifloxystrobin database or that of other strobilurin pesticides, and because endpoints 

and Points of Departure (PODs) used for risk assessment are likely to be protective of 

neurotoxicity concerns.

Trifloxystrobin exhibits low acute toxicity following single oral, dermal, and inhalation 

exposures (Toxicity Category III or IV). It is a strong dermal sensitizer and a mild dermal and 

eye irritant.
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4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

The trifloxystrobin risk assessment team evaluated the quality of the toxicity and exposure data 

and recommended that the FQPA SF be reduced to 1X because 1) the trifloxystrobin database is 

considered complete for risk assessment; 2) there is no indication of neurotoxicity following 

trifloxystrobin exposure in single or repeated dose studies; 3) there is no increased quantitative or 

qualitative susceptibility to trifloxystrobin in developmental (rats and rabbits) and reproductive 

toxicity (rats) studies; and 4) there are no uncertainties in the exposure database.

4.4.1 Completeness of the Toxicology Database

The toxicity database for trifloxystrobin is adequate for selecting toxicity endpoints and points of 

departure for risk assessment. The selected toxicity endpoints and points of departure for risk 

assessment are based on the most sensitive and relevant data.

4.4.2 Evidence of Neurotoxicity

Adverse effects were not seen up to the limit dose in an acute neurotoxicity study (the 

requirement for a subchronic neurotoxicity study has been waived as detailed in Section 4.3). 

There is no evidence of neurotoxicity in subchronic and chronic toxicity studies (rats, dogs, 

mice), in developmental toxicity studies (rats, rabbits), or in a reproductive toxicity study (rats).

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There is no indication of increased quantitative or qualitative susceptibility to trifloxystrobin in 

rats or rabbits. In the prenatal developmental study in rats, there was no developmental toxicity 

at and up to the limit dose. In the prenatal developmental study in rabbits, developmental 

toxicity was seen at a dose that was higher than the dose causing maternal toxicity. In the 

multigeneration study, offspring and parental LOAELs are at the same dose level.

4.4.4 Residual Uncertainty in the Exposure Database

The exposure databases are complete or are estimated based on data that reasonably account for 

potential exposures. The exposure assessments will not underestimate the potential dietary (food 

and drinking water) or non-dietary exposures for infants and children from the use of 

trifloxystrobin. The chronic dietary food exposure assessment was conservatively based on 

100%CT assumptions and conservative ground water drinking water modeling estimates. The 

dietary drinking water assessment utilizes water concentration values generated by models and 

associated modeling parameters which are designed to provide conservative, health protective, 

high-end estimates of water concentrations, and are not likely to be exceeded. In addition, the 

residential post-application assessment is based upon the residential SOPs employing surrogate 

study data. The Residential SOPs are based upon reasonable “worst-case” assumptions and are 

not expected to underestimate risk. These data are reliable and are not expected to underestimate 

risk to adults or children. 

4.5 Recommendation for Combining Routes of Exposure for Risk Assessment
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When common toxicity endpoints are selected for the dermal, oral, and inhalation routes of 

exposure they may be combined together. For short-term aggregate risk assessments, oral and 

inhalation routes can be combined due to the selection of a common toxicological endpoint of 

concern (the oral equivalent was used for inhalation exposure). However, 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 adverse systemic dermal hazard.

4.6 Cancer Classification and Risk Assessment Recommendation

Based on the absence of significant tumor increases in two adequate rodent carcinogenicity 

studies, trifloxystrobin is classified as: “Not likely to be Carcinogenic to Humans.” Cancer risk 

assessments do not need to be conducted.

4.7 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

The summary of toxicological doses and endpoints for human health risk assessment are 

presented below in Table 4.7.

Table 4.7 Summary of Toxicological Doses and Endpoints for Trifloxystrobin for Use in Dietary, NonOccupational, and Occupational Human Health Risk Assessmentsa

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(Females 13-

49 Only)

NOAEL = 

250 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Acute RfD = 

2.5 

mg/kg/day

aPAD = 2.5 

mg/kg/day

Developmental - Rabbit

LOAEL = 500 mg/kg/day based on increased 

fetal skeletal anomalies.

Acute Dietary

(General 

Population, 

including 

Infants and 

Children)

There were no appropriate toxicological effects attributable to a single exposure (dose) 

observed in oral toxicity studies including maternal effects in developmental studies in rats 

and rabbits. Therefore, a dose and endpoint were not identified for this risk assessment.

Chronic 

Dietary 

(All 

Populations)

NOAEL = 

3.8 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Chronic RfD 

= 0.038

mg/kg/day

cPAD = 

0.038

mg/kg/day

Two-Generation Reproduction – Rat

Maternal LOAEL = 55.3 mg/kg/day based 

on decreased body weight and

histopathological lesions in the liver, kidney 

and spleen.

Offspring LOAEL = 55.3 mg/kg/day based 

on decreased pup body weights during 

lactation.
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Table 4.7 Summary of Toxicological Doses and Endpoints for Trifloxystrobin for Use in Dietary, NonOccupational, and Occupational Human Health Risk Assessmentsa

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Incidental 

Oral 

Short-Term 

(1-30 days)

NOAEL = 

3.8 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Residential 

LOC for 

MOE = 100

Two-Generation Reproduction – Rat

Maternal LOAEL = 55.3 mg/kg/day based 

on decreased body weight and

histopathological lesions in the liver, kidney 

and spleen.

Offspring LOAEL = 55.3 mg/kg/day based 

on decreased pup body weights during 

lactation.

Dermal All 

Durations

A toxicity endpoint was not identified. Adverse systemic toxicity was not seen in 28-day 

dermal toxicity in rats at the limit dose (1000 mg/kg/day). There are no concerns for 

developmental or reproductive toxicity (including potential susceptibility issues) or 

neurotoxicity

Inhalation

All Durations

NOAEL = 

3.8 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 

1X

Residential 

LOC for 

MOE = 100

Occupational 

LOC for 

MOE = 100

Two-Generation Reproduction – Rat

Maternal LOAEL = 55.3 mg/kg/day based 

on decreased body weight and weight gain, 

decreased food consumption, liver, kidney 

and spleen effects.

Offspring LOAEL = 55.3 mg/kg/day based 

on decreased pup body weights during 

lactation.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of 

significant tumor increases in two adequate rodent carcinogenicity studies.

a 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). FQPA SF = Food Quality Protection Act 

Safety Factor. RfD = reference dose (a = acute, c = chronic). PAD = population adjusted dose (a = acute, c = 

chronic). MOE = margin of exposure. LOC = level of concern.

b Toxicity by the inhalation route is assumed to be equivalent to the oral route. A subchronic inhalation toxicity 

study is not required for trifloxystrobin at this time (Hazard and Science Policy Council memo, U. Habiba, 

TXR0056957, 05/22/2014).

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The qualitative nature of the residue in plants and livestock commodities is adequately 

understood based on acceptable metabolism studies reflecting direct application of 

trifloxystrobin to apples, cucumbers, peanuts, sugar beets, and wheat, and metabolism studies on 

goats and laying hens. HED has concluded that both trifloxystrobin and CGA-321113 are of 

concern for both regulatory and risk assessment purposes for both plant and livestock 
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commodities. HED also determined that for livestock commodities, the metabolite L7a (taurine 

conjugate of trifloxystrobin) in liver and meat byproducts should be included in the risk 

assessment. The residues of concern for dietary risk assessment and the tolerance expression are 

summarized in Table 5.1.

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression

Matrix Residues included in

Risk Assessment

Residues included in

Tolerance Expression

Plants

Primary Crop

Trifloxystrobin and CGA-321113

Rotational Crop

Livestock

Ruminant

Trifloxystrobin and CGA321113; plus Metabolite L7a 

in liver and meat byproducts

Trifloxystrobin 

and CGA-321113

Poultry Trifloxystrobin and CGA-321113

Drinking Water Trifloxystrobin 

and CGA-321113 Not Applicable

5.2 Food Residue Profile

Adequate crop field trial data have been submitted to support the requested uses on all proposed 

crops (DP422436, G. Luta, 08/06/2015). The trials reflect the proposed use pattern and the 

number and locations of the trials are acceptable. Adequate storage stability data are available to 

support the storage durations and conditions of samples of all proposed crops from the submitted 

crop field trial studies. There are no processed commodities associated with the proposed new 

uses; therefore, no new processing studies were submitted or reviewed for this petition. The 

proposed uses do not result in an increased dietary burden for livestock. The existing tolerances 

on livestock commodities are adequate. Adequate confined and field rotational crop data are 

available. HED previously concluded that the residues of concern in rotated crops are 

trifloxystrobin and CGA-321113. The available data support a 30-day plant-back interval (PBI) 

for all crops not listed on the label for direct use. 

5.3 Water Residue Profile

The environmental fate database is adequate to characterize drinking water exposure for the 

parent compound. Limited fate data are available for the degradates of trifloxystrobin. The data 

indicate that trifloxystrobin is non-persistent in soil or water with rapid degradation in aerobic 

soil. In contrast, the major degradate of concern, CGA-321113, is persistent in both soil and 

aquatic environments. Furthermore, CGA-321113 is expected to be more mobile than the parent 

compound. Model simulations show that ground water estimated drinking water concentrations 

(EDWCs) for total toxic residues of trifloxystrobin are greater than surface water EDWCs.
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EDWCs were evaluated for all proposed uses with the Pesticide Root Zone Model for Ground 

Water (PRZM-GW),

1 which models continued use of trifloxystrobin over many years

(DP422483, M. Biscoe, 03/12/2015). The most conservative EDWCs were based on an existing 

registered turf use which has the highest annual use rate (1.33 lb ai/acre) of all the proposed and 

existing uses of trifloxystrobin. Water residues were incorporated directly into the acute and 

chronic dietary assessments in the Dietary Exposure Evaluation Model – Food Commodity 

Intake Database (DEEM-FCID) food categories of “water, direct, all sources” and “water, 

indirect, all sources.” Maximum surface water EDWCs using Pesticide Root Zone Model linked 

with the Exposure Analysis Modeling System (PRZM/EXAMS) and ground water EDWCs 

using the PRZM-GW model are reported in Table 5.3. The highest estimated peak (acute) 

concentration of total toxic residues in ground water is 427 μg/L, and the highest estimated 

(chronic) concentration in ground water is 365 μg/L.

Table 5.3. Maximum Estimated Drinking Water Concentrations (EDWCs) of Total Toxic Residues of 

Trifloxystrobina

Surface Water Modelb (μg/L)

Crop Scenario Peak Exposure Annual Mean Exposure Average Annual Exposure

Peak 

1-in-10 Year

Chronic 

1-in-10 Year 30-year Annual Average

Pennsylvania Turf scenario 

Aerial Application 29 ppb 23 ppb 19 ppb

Ground Water Modelc (μg/L)

Crop Scenario Peak Post-Breakthrough Average

Wisconsin Corn scenario 

Ground Application 427 ppb 365 ppb

a EDWC modeling includes total toxic residue (TTR) of trifloxystrobin and its major degradate, CGA-32113, based 

on 1.33 lb ai/A for turf (Trifloxystrobin Flowable Fungicide, EPA Reg. No. 264-989). The highest estimated 

drinking water concentration are bolded.

b Highest EDWCs generated using PRZM/EXAMS model. PCA of 0.91 adjusted for aerial application.

c Highest EDWCs generated using PRZM-GW 30-year simulation model.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Acute and chronic dietary (food and drinking water) exposure and risk assessments were

conducted using the DEEM-FCID Version 3.16. This model uses 2003-2008 food consumption 

data from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition 

Examination Survey, What We Eat in America (NHANES/WWEIA).

The acute females 13-49 assessment was based on the assumption of tolerance level residues for 

all commodities while the chronic assessment incorporated some average residues. Both 

assessments assumed 100%CT. For the dietary assessments, a value of 0.20 ppm was added to 

the recommended tolerance for liver to account for the Metabolite L7a; therefore, meat 

byproducts and liver of cattle, goats, horses, and sheep were assessed in the dietary assessments 

at 0.3 ppm. The maximum theoretical dietary burden was lower for pork, except for pork liver, 

 1 PRZM-GW was approved for standard use in drinking water assessments as a Tier I/II exposure tool (12/2012). 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

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than for these other commodities. Therefore, pork was included in the DEEM at the established 

tolerance level of 0.05 ppm; pork, liver was included at 0.16 ppm (DP267787, L. Cheng, 

01/17/2002). A separate tolerance was set for grape, raisin; therefore, the processing factor for 

this commodity was set at 1. For all other processed commodities, DEEM 7.81 default 

processing factors were used. Residue reduction data on strawberries from a single trial were 

previously provided which demonstrated that residues of trifloxystrobin and CGA-321113 

declined in/on strawberries after washing and cooking. The default processing factor of 1 was 

retained since the exposure estimates are below HED’s LOC.

The chronic dietary assessment was refined by using average residues for the proposed crop 

groups and apple, grape, orange, rice, and pear commodities. The averages for the new 

commodities were calculated in the memo summarizing the tolerance assessment (DP422436, G. 

Luta, 08/06/2015). A summary of the residue data used to calculate the average residues for rice, 

apple, grape, and orange, commodities is attached to this memo. Residue data from apple field 

trials were used for all pome fruits since averages were higher from apples than pears. The limit 

of quantitation (LOQ) value was used for all non-detectable samples.

The acute drinking water estimate of 427 μg/L was directly incorporated into the acute 

assessment. The chronic drinking water estimate of 365 μg/L was directly incorporated into the 

chronic assessment.

5.4.2 Acute Dietary Risk Assessment

There were no appropriate toxicological effects attributable to a single exposure (dose) for the 

general population; therefore, a dose and endpoint were not identified and a dietary exposure 

assessment was not conducted. An acute endpoint was identified for females 13-49 years old. 

Therefore, an acute dietary assessment was conducted for this population subgroup.

The results of the acute dietary (food and drinking water) analysis indicate that exposure and risk 

does not exceed HED’s LOC for females 13-49 years old. At the 95th percentile of exposure, the 

dietary exposure estimate for food and drinking water is estimated at 3.1% of the aPAD for the 

females 13-49 years old.

5.4.3 Chronic Dietary Risk Assessment

The results of the chronic dietary (food and drinking water) analysis indicate that exposure and 

risk estimates are not of concern to HED for the U.S. population and all population subgroups. 

The dietary exposure for food and drinking water is estimated at 34% of the cPAD for the 

general U.S. population and 71% for all infants (<1 year old), the most highly exposed 

population subgroup. Drinking water residues make up the majority of the dietary exposure 

contribution in the chronic risk estimates. The results of the chronic dietary exposure analyses 

are reported in Table 5.4.5.

5.4.4 Cancer Dietary Risk Assessment
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Trifloxystrobin is classified as “not likely to be carcinogenic to humans;” therefore, cancer risk 

was not assessed.

5.4.5 Summary Table

Table 5.4.5. Summary of Dietary Exposure and Risk for Trifloxystrobin (cPAD = 0.038 mg/kg/day)a

Population Subgroup Acute Dietary Exposure Estimates

(Food and Drinking Water)

Chronic Dietary Exposure Estimates

(Food and Drinking Water)

mg/kg/day % aPAD mg/kg/day % cPAD

General U.S. Population

N/Ab

0.013028 34

All Infants (< 1 year old) 0.026821 71

Children 1-2 years old 0.024642 65

Children 3-5 years old 0.020301 53

Children 6-12 years old 0.013125 34

Youth 13-19 years old 0.009489 25

Adults 20-49 years old 0.012339 32

Adults 50-99 years old 0.012408 33

Females 13-49 years old 0.077271 3.1 0.012318 32

a The population subgroups with the greatest exposure are bolded.

b N/A = Not Applicable; an acute dietary endpoint was not identified for these population subgroups.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are no proposed residential uses at this time; however, there are existing residential turf 

and ornamental uses that have been previously assessed (DP413713, N. Tsaur, 05/15/2014). 

The assessment of all registered residential products does not result in any residential handler or 

post-application risk estimates of concern. Residential handler exposure is expected to be shortterm only. Intermediate-term exposures are not likely because of the intermittent nature of 

applications by homeowners. The quantitative exposure/risk assessment developed for 

residential handlers is based on various exposure scenarios that involve mixing/loading/applying 

various formulations with manually pressurized handguns, hose-end sprayers, backpack sprayers, 

and sprinkler cans. Short-term residential handler inhalation MOEs range from 8,100 to 

170,000,000. Short-term incidental-oral post-application MOEs for all residential scenarios 

range from 730 to 330,000. Dermal handler risk assessments were not conducted because an 

adverse systemic dermal hazard was not identified for trifloxystrobin. Incidental oral granule 

ingestion is not applicable because there is no endpoint identified for the acute dietary duration

applicable to children. Appendix D summarizes all assessed residential exposure and risk 

estimates.

6.1 Combined Residential Risk Estimates

HED combines risk estimates resulting from separate post-application exposure scenarios when 

it is likely they can occur simultaneously based on the use pattern and the behavior associated 

with the exposed population and when the toxicological effects are similar. However, the

incidental oral scenarios (i.e., hand-to-mouth, object-to-mouth, and soil ingestion) should be 
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considered inter-related and it is likely that they occur interspersed amongst each other across 

time. Combining all three of these scenarios would be overly-conservative because of the 

conservative nature of each individual assessment. Therefore, the hand-to-mouth postapplication exposure scenario for children 1 to < 2 years old is considered a protective estimate 

of children’s exposure to pesticides used on turf.

6.2 Recommendations for Aggregate Assessment

For the purpose of the trifloxystrobin human health risk assessment, a summary of the worst-case 

residential exposure estimates are provided in Table 6.2. All short-term residential handler and 

post-application exposure estimates resulted in MOEs greater than 100, and were not of concern.

Table 6.2. Scenarios Recommended for Aggregate Risk Assessment of Trifloxystrobin (Short-Term)

Scenario Dosea MOE

mg/kg/day LOC = 100

Adults

Handler: Inhalation Exposure

(Manually-Pressurized Handwand or Backpack Sprayer Application 

of Water Dispersible Granule Formulation to Residential Turf)

0.00047 8,100

Children 1 to < 2 years old

Post-Application: Hand-to-Mouth Exposure

(Liquid Application to Residential Lawn) 0.0052 730

a Handler scenario represents high-end handler exposure (DP413713, N. Tsaur, 05/15/2014).

b Post-application MOE represents high-end incidental oral exposure (DP413713, N. Tsaur, 05/15/2014).

c MOE = NOAEL ÷ Average Daily Dose. Inhalation NOAEL = 3.8 mg/kg/day. Incidental Oral NOAEL = 3.8 mg/kg/day.

6.3 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/2009/120109meeting.html). The 

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

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). 

During Registration Review, the agency will utilize this analysis to determine if data (i.e. flux 

studies, route-specific inhalation toxicological studies) or further analysis is required for 

trifloxystrobin.

6.4 Non-Occupational Spray Drift Exposure and Risk Estimates 

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

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g. groundboom and airblast) 

employed for trifloxystrobin. The agency has been working with the Spray Drift Task Force (a 

task force composed of various registrants which was developed as a result of a Data Call-In 

issued by EPA), EPA Regional Offices, and State Lead Agencies for pesticide regulation, and 
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other parties to develop the best spray drift management practices (see the agency’s Spray Drift 

website for more information). 2

 The agency has also developed a policy on how to 

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

pesticides. The potential for spray drift will be quantitatively evaluated for each pesticide during 

the Registration Review process which ensures that all uses for that pesticide will be considered 

concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures 

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

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

of indirect non-occupational exposure to drift.

7.0 Aggregate Exposure/Risk Characterization

HED aggregates (adds) pesticide exposures and risks from three major sources: food, drinking 

water, and residential exposures. In an aggregate assessment, exposures from relevant sources 

are added together and compared to quantitative estimates of hazard (e.g. a NOAEL or PAD), or 

the risks themselves can be aggregated. When aggregating exposures and risks from various 

sources, HED considers both the route and duration of exposure. For trifloxystrobin, potential 

exposures from food, drinking water, and residential scenarios were aggregated.

7.1 Acute Aggregate Risk

There were no appropriate toxicological effects attributable to a single exposure (dose) for the 

general population; therefore, a dose and endpoint were not identified for this risk assessment. 

The aPAD for females 13-49 years old was 2.5 mg/kg/day. To assess the aggregate acute risk, 

EDWCs were incorporated directly into the dietary exposure analysis. Refer to Section 5.4.1 for 

this risk estimate.

7.2 Short-Term Aggregate Risk

There is potential short-term exposure to trifloxystrobin via dietary (which is considered 

background exposure) and residential (which is considered primary) pathways. For adults, these 

pathways lead to exposure via oral (background) as well as dermal and inhalation (primary) 

routes. For children, these pathways lead to exposure via the oral (background) as well as 

incidental oral and dermal (primary) routes. For trifloxystrobin, dermal routes of exposure are 

not combined into an aggregate risk estimate because there are no adverse systemic hazards via 

the dermal route. Thus, only adult inhalation and children incidental oral aggregate MOEs are 

presented. Table 7.2 shows that all MOEs are greater than 100, and aggregate risk estimates are 

not of concern. The children’s aggregate estimate for incidental oral exposure only incorporates 

hand-to-mouth oral exposure because it is considered to be a conservative upper bound estimate 

of oral post-application exposure. Additionally, the dietary exposure estimates (food and water) 

are conservative. Further refinement using additional anticipated residues and empirical 

processing factors may need to be incorporated in future assessments.

 2 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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Table 7.2. Short-Term Aggregate Risk Calculations for Trifloxystrobin

Population

NOAEL

LOCa

Average 

Food and 

Water 

Exposure

Residential

Handler

Exposureb

Residential 

PostApplication

Exposurec

Total 

Exposured

Aggregate 

MOE (food, 

water, and 

residential)e

mg/kg/day mg/kg/day mg/kg/day mg/kg/day mg/kg/day

Adult 3.8 100 0.012408f 0.00047 NAg 0.01288 290

Children

1-2 years old

(Oral Exposure)

3.8 100 0.024670 NAg 0.0052 0.029870 130

a The LOC is based on inter- and intra- species uncertainty factors which total 100X.

b Residential handler exposure based on adult handler inhalation only, of manually-pressurized handwand or 

backpack sprayer application of water dispersible granule formulation to residential turf (see Table 6.2).

c Residential post-application exposure based on children incidental oral only, of hand-to-mouth exposure 

following liquid application to residential lawn (see Table 6.2).

d Total Exposure = Average Food and Water Exposure + Residential Exposure.

e Aggregate MOE = NOAEL / (Avg Food & Water Exposure + Residential Exposure).

f Adult subpopulation of “Adults 50-99” was selected from the chronic dietary exposure assessment as the most 

protective adult subpopulation.

g NA = Not Applicable.

7.3 Intermediate-Term Aggregate Risk

An intermediate-term aggregate risk assessment (1 to 6 months of exposure to trifloxystrobin 

residues from food, drinking water, and residential pesticide uses) is not expected to occur based 

on the intermittent nature of homeowner applications, and the short soil half-life (about 2 days). 

Therefore, an intermediate-term aggregate risk assessment was not performed.

7.4 Chronic Aggregate Risk

There is potential chronic exposure via dietary (food and drinking water) exposure. Refer to 

Section 5.4.2.

7.5 Cancer Aggregate Risk

Trifloxystrobin is classified as “not likely to be carcinogenic to humans;” therefore, an aggregate 

cancer assessment has not been conducted.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to trifloxystrobin and any other substances and trifloxystrobin does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that trifloxystrobin has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 
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mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

Although there are occupational exposures associated with all of the proposed uses, the most 

recent occupational risk assessment is protective of the proposed uses, and a new occupational 

risk assessment was not conducted for this action (DP413713, N. Tsaur, 05/15/2014). The most 

recent assessment was for typical and high acreage field crops treated at a maximum single 

application rate of 0.12 lb ai/A via ground, aerial, and chemigation equipment. The highest 

application rate of the newly proposed crops to be applied to typical and high acreage field crops 

is also 0.12 lb ai/A. Thus, a new occupational risk assessment is not needed because the 

previous assessment already covers the proposed uses; the occupational risk estimates were not 

of concern. It should be noted that HED previously required a TTR study to be submitted for the 

residential use on turf (the lowest MOE of 730 was based on hand-to-mouth postapplication to 

residential turf treated with a liquid formulation of trifloxystrobin).

Trifloxystrobin is classified as Toxicity Category IV via the dermal route. It is a mild irritant to 

eyes and skin, and it is a strong dermal 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 12-hour REI on the 

proposed label is adequate to protect workers.

10.0 References

Biscoe, Melanie. 03/12/2015. DP Barcode 422483. “Trifloxystrobin: Drinking Water Exposure 

Assessment in Support of New Uses on Several Vegetable and Small Fruit Crop Groups

(Leafy Greens, Brassica, Herbs, Spices, Tuberous and Corm Vegetables, Small Fruit of 

Climbing Vines, and Low-Growing Berries).”

Luta, Gabriela. 08/06/2015. DP Barcode 422436. “Trifloxystrobin. Application for Section 3 

Registration for Uses on Tuberous and Corm Vegetables (Subgroup 1C), Leafy Greens 

(Subgroup 4A), Leafy Petioles (Subgroup 4B), Head and Stem Brassica Vegetables 

(Subgroup 5A), Leafy Brassica Greens (Subgroup 5B), Herbs (Subgroup 19A), and Spices 

(Subgroup 19B). Summary of Analytical Chemistry and Residue Data.”

Luta, Gabriela. 11/17/2015. DP Barcode 428501. “Trifloxystrobin. Evaluation of Proposed 

Tolerances for Tuberous and Corm Vegetables (Subgroup 1C), Leafy Greens (Subgroup 4A), 

Leafy Petioles (Subgroup 4B), Head and Stem Brassica Vegetables (Subgroup 5A), Leafy 

Brassica Greens (Subgroup 5B), Small Fruit Vine Climbing (Except Fuzzy Kiwifruit) 

(Subgroup 13-07F), Low Growing Berry (Subgroup 13-07G), Herbs (Subgroup 19A), and 

Spices (Subgroup 19B).

Negussie, Meheret. 11/24/2015. DP Barcode 422978. “Trifloxystrobin. Acute and Chronic 

Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for Uses on
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

Page 25 of 32

Leafy Vegetables, Brassica Vegetables, Herbs, Spices, Crop Subgroup 1C, Small Fruit Vine 

Climbing (Subgroup 13-07F) and Low Growing Berries (Subgroup 13-07G).”

Tsaur, Nancy. 06/03/2014. DP Barcode 413109. “Trifloxystrobin. Aggregate Human Health 

Risk Assessment for the Proposed New Uses on Chickpea, Dry Peas, and Lentils with 

Updated Residential Risk Estimates of All Existing Residential Uses (Lawns/Turf; Gardens 

and Trees).”

Tsaur, Nancy. 05/15/2014. DP Barcode 413713. “Trifloxystrobin. Occupational Exposure and 

Risk Assessment for the Proposed New Uses on Chickpea, Dry Peas, and Lentils with An 

Updated Residential Exposure Assessment of All Existing Residential Uses.”
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

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Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR § 158.555) for food use for trifloxystrobin are in Table A.1. Use of 

the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A.1. Satisfaction of Trifloxystrobin Toxicology Data Requirements

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization .....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent).........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

CRa

waivedb

yes

yes

yes

-

-

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent) ............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse) ...................................................

870.4300 Chronic/Oncogenicity....................................................

- 

yes

-

yes

yes

-

yes

-

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotoxicity Screening Battery (rat) .................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Develop. Neurotoxicity .................................................

no

no

yes

yes

CRc

-

-

yes

nod

-

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration........................................................

870.7800 Immunotoxicity .............................................................

yes

yes

yes

yes

yes

yes

a Conditionally required.

b A subchronic inhalation toxicity study has been waived for trifloxystrobin at this time (Hazard and Science Policy 

Council memo, TXR0056957, U. Habiba, 05/22/2014).

c Conditional requirement pending submission of acceptable guideline acute and subchronic neurotoxicity batteries.

d A subchronic neurotoxicity study has been waived for trifloxystrobin at this time (Hazard and Science Policy 

Council memo, TXR0056150, D. Smegal, 01/05/2012)
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

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A.2 Toxicity Profile of Trifloxystrobin Technical

Table A.2.1. Trifloxystrobin Acute Toxicity Profile

Guideline No. Study Type MRID Results Toxicity 

Category

870.1100 Acute Oral – Rats 44496622

44496623 LD50 > 5 g/kg IV

870.1200 Acute Dermal – Rabbits 44496626

44496627 LD50 > 2 g/kg IV

870.1300 Acute Inhalation – Rats 44496630 LC50 > 4.65 mg/L IV

870.2400 Primary Eye Irritation – Rabbits 44496632 mild irritant III

870.2500 Primary Skin Irritation – Rabbits 44496635 mild irritant IV

870.2600 Dermal Sensitization – Guinea Pigs 44496637

44496638 strong sensitizer N/A

Table A.2.2. Trifloxystrobin Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.3100 28-Day rangefinding oral 

toxicity (rat)

44496643 (1994)

0, 200, 1000, 4000, or 

12000 ppm

M: 0, 16.5, 84.4, 337, 

1,074 mg/kg/day

F: 0, 16.4, 84.1, 327, or 

1,005 mg/kg/day

NOAEL = 84.1 mg/kg/day

LOAEL = 327 mg/kg/day based on decreased body 

weight and increased relative liver weight.

870.3100 90-Day oral 

toxicity (rat)

44496701 (1995)

Acceptable/Guideline

0, 100, 500, 2000, or 

8000 (F only) ppm

M: 0, 6.44, 30.6, or 127 

mg/kg/day

F: 0, 6.76, 32.8, 133, or 

618 mg/kg/day

NOAEL = 30.6 mg/kg/day

LOAEL =127 mg/kg/day based on decreased body 

weight (males), hypertrophy of hepatocytes (males), 

and pancreatic atrophy.

870.3100 90-Day oral 

toxicity (mouse)

44496641(1994) 

Acceptable/Guideline

0, 500, 2000, 7000 ppm

M: 0, 76.9, 315, or 1,275 

mg/kg/day

F: 0, 110, 425, 1649 

mg/kg/day

NOAEL = 76.9 mg/kg/day

LOAEL = 315 mg/kg/day based on increased liver 

weights and necrosis of hepatocytes.

870.3150 90-Day oral 

toxicity (dog) 

[capsule]

44496702 (1994)

Acceptable/Guideline

0, 5, 30, 150, or 500 

mg/kg/day

NOAEL = 30 mg/kg/day

LOAEL = 150 mg/kg/day based on increased liver 

weight and hepatocyte hypertrophy; increased 

incidence of diarrhea and vomiting. 

870.3150

28-Day 

subchronic 

range-finding 

oral toxicity 

(dog) [capsule]

44496642 (1994)

Unacceptable/nonguideline

(2 dog/sex/dose)

0, 20, 50, 150 mg/kg/day

NOAEL=50 mg/kg/day

LOAEL= 150 mg/kg/day based on increased 

incidence of diarrhea and vomiting and body weight 

reduction.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

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Table A.2.2. Trifloxystrobin Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.3200 28-Day dermal 

toxicity (rat)

44496703 (1996)

Acceptable/Guideline

0, 10, 100, 1000 

mg/kg/day

NOAEL = 1000 mg/kg/day.

LOAEL > 1000 mg/kg/day; a LOAEL was not 

established. Increases in liver and kidney weights 

observed at this dose were not accompanied with 

any histopathological correlates and not considered 

adverse.

870.3700a Prenatal 

developmental in 

(rat) [gavage]

44496708 (1995)

Acceptable/Guideline

0, 10, 100, 300 

mg/kg/day

Maternal NOAEL = 10 mg/kg/day. 

Maternal LOAEL = 100 mg/kg/day based on 

decreased body weight gain and food consumption.

Developmental NOAEL = 1000 mg/kg/day (HDT).

870.3700b Prenatal 

developmental in 

(rabbit) [gavage]

44496709 (1994)

Acceptable/Guideline

0, 10, 50, 250, 500 

mg/kg/day

Maternal NOAEL = 10 mg/kg/day. 

Maternal LOAEL of 50 mg/kg/day based on

decreased body weights and body weight gain, food 

consumption and efficiency.

Developmental NOAEL = 250 mg/kg/day. 

Developmental LOAEL = 500 mg/kg/day based

skeletal anomalies (fused sternabrae #3 & #4).

870.3800

Multigenerational 

reproduction and 

fertility effects

(rat)

44496710 (1997)

Acceptable/Guideline

0, 50, 750, 1500 ppm

M: 0, 3.8, 55.3, 110.6 

mg/kg/day

F: 4.1, 58, 123.1 

mg/kg/day

Parental NOAEL = 3.8 mg/kg/day. 

Parental LOAEL = 55.3 mg/kg/day based on

decreased body weight and weight gain, decreased 

food consumption, liver, kidney and spleen effects.

Offspring NOAEL= 3.8 mg/kg/day

Offspring LOAEL = 55.3 mg/kg/day based on 

decreased pup body weights during lactation.

Reproductive NOAEL = 110.6 mg/kg/day (HDT).

870.4100b Chronic toxicity 

(dog) [capsule]

44496704 (1997)

Acceptable/Guideline

0. 2, 5, 50, 200 

mg/kg/day

NOAEL = 5 mg/kg/day. 

LOAEL = 50 mg/kg/day based on increased clinical 

signs, increased liver weight and hepatocellular 

hypertrophy. 

870.4200b Carcinogenicity

(mouse)

44496705 (1997)

Acceptable/Guideline

0, 30, 300, 1000, 2000 

ppm

M: 0, 3.9, 39.4, 131.1, 

274 mg/kg/day

F: 0, 3.51, 35.7, 124.1, 

274 mg/kg/day

NOAEL = 39.4 mg/kg/day

LOAEL =131.1 mg/kg/day based on liver effects 

(single cell necrosis, hepatocellular hypertrophy).

There was non-statistically significant and non-dose 

related increase in lymphoma incidence. 

Trifloxystrobin is classified as “Not Likely to be 

Carcinogenic to Humans.”

870.4300 Carcinogenicity 

chronic toxicity

(rat)

44496711 (1997)

Acceptable/Guideline

0, 50, 250, 750, 1500 

ppm

M:0, 1.95, 9.81,29.7, 

62.2 mg/kg/day

F: 0, 2.22, 11.37, 34.5, 

72.8 mg/kg/day

NOAEL = 9.81 mg/kg/day

LOAEL= 29.7 mg/kg/day based on decreased body 

weight and body weight gain.

No increase in tumor incidence. 

870.5100

In vitro bacterial 

reverse gene 

mutation -

Salmonella

44496712

44496715 

44496716

44496717

Acceptable/Guideline

Negative
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

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Table A.2.2. Trifloxystrobin Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (year)/ Classification /Doses Results

870.5300

Gene Mutation in 

Chinese Hamster 

Cultured V-79

44496713

Acceptable/Guideline Positive

870.5385

Structural 

Chromosome 

Aberration -

Micronucleus -

mouse

44496714

Acceptable/Guideline Negative

870.5385

Structural 

Chromosome 

Aberration -

Cytogenetics -

Chinese Hamster

44496718

Acceptable/Guideline Negative

870.5500 DNA Repair-Rat 

hepatocytes

44496719

Acceptable/Guideline Negative

870.6200a

Acute oral 

neurotoxicity 

screening battery 

(rat)

Acute oral rangefinding 

neurotoxicity 

(rat)

44496640 (1977)

Acceptable/Nonguideline

0, 2000 mg/kg/day

44840802 (1997)

0, 1000, 2000, 3500 

mg/kg/day (provides 

supplemental 

information).

Study useful for risk assessment and does not need

to be repeated (TXR0056150, D. Smegal, 

01/05/2012).

NOAEL and LOAEL could not be determined

because the data on females were missing.

Piloerection and reduced activity were often found 

in 2000 and 3500 mg/kg test animals, and the 

effects peaked at 6 to 8 hours post dosing. No 

mortality and no effects on food consumption and 

body weights were found.

870.7485

Metabolism & 

pharmacokinetics 

(rat)

44496722 (1997)

44496821 (1996)

Acceptable/Guideline

0.5, 100 mg/kg/day

Oral administration of trifloxystrobin to rats 

resulted in 56% and 65% of the administered dose 

absorbed by male and female rats, respectively. The 

time to maximal blood concentration was 12-24 

hours. 41% and 47% of the administered dose was 

found in the bile of males and females respectively. 

Highest residues were found in liver, kidneys, 

spleen and blood. Majority of the administered 

radioactivity was eliminated in the feces. Less than 

0.1% of the administered dose was found in the 

expired air. Total tissue and carcass content was 

0.3-0.5% of the administered dose. Parent 

compound was extensively metabolized to 

approximately 35 metabolites. 

870.7800 Immunotoxicity 

(male rat)

48856301 (2012)

Acceptable/Guideline

0, 200, 1000, 4000 ppm 

0, 14.2, 70.5, 263 mg/kg 

bw/day

Systemic NOAEL = 70.5 mg/kg/day

Systemic LOAEL = 263 mg/kg bw/day based on 

decreased body weight, body weight gain, and feed 

consumption.

Immunotoxicity NOAEL = 263 mg/kg/day

Immunotoxicity LOAEL is not established
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

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Appendix B. Physical/Chemical Properties

Table B. Physico-Chemical Properties of Trifloxystrobin

Parameter Value Reference

Melting Point/Range 72.9oC

MRID 44502801

pH (25oC) 7.7 in 1% w/w aqueous dispersion

Density (21oC) 1.36 g/cm2

Water Solubility (20oC) 0.00061 g/L

Solvent Solubility (g/L at 25°C)

methanol 76

acetone >500

ethyl acetate >500

n-hexane 11

dichloromethane >500

toluene 500

n-octanol 18

Vapor Pressure (25°C) 3.4 x 10-6 Pa, 2.55 x 10-7 mm Hg

Dissociation Constant (pKa) none at pH of 2-12

Octanol/Water Partition Coefficient 

(25oC) Log(KOW) 4.5

UV/Visible Absorption Spectrum

17,500 at 250.7 μm (neutral)

17,300 at 250.2 μm (acidic)

15,900 at 252.3 μm (basic)

Appendix C. Review of Human Research

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 studies, which comprise the 

Pesticide Handlers Exposure Databased (PHED) and Agricultural Handlers Exposure Task Force 

(AHETF), have been determined to require a review of their ethical conduct and have received 

that review. In this assessment, PHED and AHETF data were used to assess mixing, loading, 

and applying a liquid formulation of trifloxystrobin.

 

Studies reviewed by the Human Studies Review Board: None.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

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Appendix D. Residential Exposure/Risk Summary Table

Table D.1. Short-Term Residential Handler Exposure and Risk Estimates for Trifloxystrobin

Application on Residential Turf and Ornamentalsa

Exposure Scenario Application 

Rateb

Amount 

Handled or 

Area Treated 

Dailyc

Baseline 

Inhalation Unit 

Exposured

Baseline 

Inhalation Dosee

Inhalation 

Baseline 

MOEf

mg/lb ai mg/kg/day LOC = 100

Liquid Formulation on Turf

Manually-Pressurized 

Handwand

0.034

lb ai/gal

5

gallons 0.018 0.000038 99,000

Hose-End Sprayer 0.34

lb ai/acre

0.50

acres 0.022 0.000047 81,000

Backpack

Sprayer

0.034

lb ai/gal

5

gallons 0.14 0.0003 13,000

Sprinkler Can 0.0000078

lb ai/sq ft

1,000

sq ft 0.022 0.0000021 1,800,000

Water Soluble Packaging on Turf

Manually-Pressurized 

Handwand

0.0068

lb ai/gal

5

gallons 0.018 0.0000077 500,000

Hose-End Sprayer 0.34

lb ai/acre

0.50

acres 0.034 0.000072 53,000

Backpack

Sprayer

0.068

lb ai/gal

5

gallons 0.018 0.0000077 500,000

Sprinkler Can 0.0000078 1,000

sq ft 0.034 0.0000033 1,100,000

Water Dispersible Granules Formulation on Turf

Manually-Pressurized 

Handwand

0.0068

lb ai/gal

5

gallons 1.1 0.00047 8,100

Hose-End Sprayer 0.34

lb ai/acre

0.50

acres 0.022 0.000047 81,000

Backpack

Sprayer

0.0068

lb ai/gal

5

gallons 1.1 0.00047 8,100

Sprinkler Can 0.0000078

lb ai/sq ft

1,000

sq ft 0.022 0.0000021 1,800,000

Water Soluble Packaging on Ornamentals

Manually-Pressurized 

Handwand

0.00000094

lb ai/sq ft

1,200

sq ft 0.018 0.00000025 15,000,000

0.00047

lb ai/gal

5

gallons 0.018 0.00000053 7,200,000

Hose-End Sprayer

0.00000094

lb ai/sq ft

1,200

sq ft 0.034 0.00000048 7,900,000

0.00047

lb ai/gal

11

gallons 0.034 0.0000022 1,700,000

Backpack

Sprayer

0.00000094

lb ai/sq ft

1,200

sq ft 0.018 0.00000025 15,000,000

0.00047

lb ai/gal

5

gallons 0.018 0.00000053 7,200,000

Sprinkler Can

0.00000094

lb ai/sq ft

1,200

sq ft 0.034 0.00000048 7,900,000

0.00047

lb ai/gal

5

gallons 0.034 0.000001 3,800,000

Water Dispensable Granules Formulation on Ornamentals

Manually-Pressurized 

Handwand

0.0000011

lb ai/sq ft

1,200

sq ft 1.1 0.000018 210,000

0.0013

lb ai/gal

5

gallons 1.1 0.000089 43,000

Hose-End Sprayer

0.0000011

lb ai/sq ft

1,200

sq ft 0.0014 0.000000023 170,000,000

0.0013

lb ai/gal

11

gallons 0.0014 0.00000025 15,000,000
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D422974

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Table D.1. Short-Term Residential Handler Exposure and Risk Estimates for Trifloxystrobin

Application on Residential Turf and Ornamentalsa

Exposure Scenario Application 

Rateb

Amount 

Handled or 

Area Treated 

Dailyc

Baseline 

Inhalation Unit 

Exposured

Baseline 

Inhalation Dosee

Inhalation 

Baseline 

MOEf

mg/lb ai mg/kg/day LOC = 100

Backpack

Sprayer

0.0000011

lb ai/sq ft

1,200

sq ft 1.1 0.000018 210,000

0.0013

lb ai/gal

5

gallons 1.1 0.000089 43,000

Sprinkler Can

0.0000011

lb ai/sq ft

1,200

sq ft 0.0014 0.000000023 170,000,000

0.0013

lb ai/gal

5

gallons 0.0014 0.00000011 33,000,000

a Bolded values represent the high-end exposure scenario recommended for aggregate risk calculations.

b Application Rates based on maximum application rates of registered residential turf and ornamental uses for trifloxystrobin.

c Based on HED’s SOPs: Lawns/Turf and Gardens and Trees (January 2012).

d Baseline Inhalation: no respirator. 

e Dose (mg/kg/day) = daily unit exposure (mg/lb ai) × application rate (lb ai per gallons, square feet, or acres) × amount handled 

or area treated (gallons, square feet, or acres per day) ÷ body weight (80 kg). No inhalation absorption factor.

f MOE = NOAEL ÷ daily dose (mg/kg/day). ST Inhalation NOAEL = 3.8 mg/kg/day. Level of concern = 100.

Table D.2. Short-Term Residential Post-Application Exposure and Risk Estimates for Trifloxystrobin on 

Turf and Ornamentalsa

Lifestage Post-Application Exposure Scenario Doseb

MOEc

mg/kg/day

Liquid Formulation on Turf

max single application rate: 0.34 lb ai/A

Child 1 to < 2 years old Oral

Hand to Mouth 0.0052 730

Object to Mouth 0.00016 24,000

Soil Ingestion 0.000012 330,000

Granular Formulation on Turf

max single application rate: 0.34 lb ai/A

Child 1 to < 2 years old Orald

Hand to Mouth 0.00051 7,400

Object to Mouth 0.000031 120,000

Soil Ingestion 0.000012 330,000

a Bolded values represent the high-end exposure scenario recommended for aggregate risk calculations.

b Hand-to-Mouth Dose = hand residue loading (mg/cm2) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm2) 

× exposure time (1.5 hrs/day) × # of replenishment intervals/hr (4 int/hr) × (1-((1-saliva extraction factor (0.5))^(Number of 

hand-to-mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (11 kg).

Object-to-Mouth Dose = object residue loading (μg/cm2) × unit conversion factor (0.001 mg/μg) × object surface area mouthed

/ event (10 cm2/event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1-((1- saliva extraction factor 

(0.50))^(# Object-to-Mouth Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr)) ÷ body weight (11 kg).

Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg).

c MOE = NOAEL ÷ Daily Dose (mg/kg/day). Incidental Oral NOAEL= 3.8 mg/kg/day. Level of concern = 100.

d Incidental Granule Ingestion is not applicable because there is no endpoint identified for the acute dietary duration.