TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 1 of 36

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

DATE: June 10, 2014

SUBJECT: 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).

PC Code: 129112 DP Barcode: D413109

Decision No.: 478982 Registration No.: 264-1055

Petition No.: 3F8180 Regulatory Action: Section 3 Registration

Case No.: NA Risk Assessment Type: Single Chemical/Aggregate

TXR No.: NA CAS No.: 141517-21-7

MRID No.: NA 40 CFR: §180.555

FROM: Nancy Keller, Chemist, Risk Assessor

Meheret Negussie, Chemist

Myron Ottley, Senior Toxicologist

Risk Assessment Branch 3

Health Effects Division (7509P)

THROUGH: Christine Olinger, Branch Chief

Risk Assessment Branch 3

Health Effects Division (7509P)

TO: Marcel Howard

Fungicides Branch (FB)

Registration Division (7505P)

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

evaluation of the proposed new agricultural uses of trifloxystrobin on chickpea, dry peas, and 

lentils. A summary of the findings and an assessment of human health risk resulting from the 

proposed and registered uses of trifloxystrobin are provided in this document.

The toxicology and hazard database review was conducted by Myron Ottley; the residue 

chemistry review and dietary risk assessment were conducted by Meheret Negussie; the 

occupational/residential exposure and aggregate risk assessments were conducted by Nancy

Tsaur.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 2 of 36

Table of Contents

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

2.0 HED Recommendations.......................................................................................................6

2.1 Data Deficiencies ............................................................................................................ 6

2.2 Tolerance Considerations.............................................................................................. 6

2.2.1 Enforcement Analytical Method................................................................................... 6

2.2.3 Revisions to Petitioned-For Tolerances........................................................................ 7

2.2.4 International Harmonization ........................................................................................ 7

2.2.5 Label Recommendation................................................................................................. 8

3.0 Introduction...........................................................................................................................8

3.1 Chemical Identity ........................................................................................................... 8

3.2 Physical/Chemical Characteristics ............................................................................... 9

3.3 Pesticide Use Pattern...................................................................................................... 9

3.4 Anticipated Exposure Pathways................................................................................... 9

3.5 Consideration of Environmental Justice.................................................................... 10

4.0 Hazard Characterization and Dose-Response Assessment.............................................10

4.1 Toxicology Studies Available for Analysis................................................................. 10

4.2 Absorption, Distribution, Metabolism and Excretion (ADME) .............................. 10

4.3 Toxicological Effects .................................................................................................... 11

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 12

4.4.1 Completeness of the Toxicology Database.......................................................... 12

4.4.2 Evidence of Neurotoxicity .................................................................................... 12

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal .... 12

4.4.4 Residual Uncertainty in the Exposure Database................................................ 13

4.5 Toxicity Endpoint and Point of Departure Selection................................................ 13

4.5.1 Recommendation for Combining Routes of Exposure for Risk Assessment... 13

4.5.2 Cancer Classification and Risk Assessment Recommendation ........................ 13

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

Assessment........................................................................................................................... 14

5.0 Dietary Exposure and Risk Assessment............................................................................15

5.1 Residues of Concern Summary and Rationale.......................................................... 15

5.2 Food Residue Profile .................................................................................................... 16

5.3 Water Residue Profile.................................................................................................. 16

5.4 Dietary Risk Assessment.............................................................................................. 17

5.4.1 Description of Residue Data Used in Dietary Assessment ................................ 17

5.4.2 Acute Dietary Risk Assessment ........................................................................... 18

5.4.3 Chronic Dietary Risk Assessment ....................................................................... 18

5.4.4 Cancer Dietary Risk Assessment......................................................................... 18

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................................19

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

6.2 Recommendations for Aggregate Assessment........................................................... 20

6.3 Residential Bystander Post-Application Inhalation Exposure ................................ 20

6.4 Spray Drift.................................................................................................................... 21

7.0 Aggregate Exposure/Risk Characterization.....................................................................21

7.1 Acute Aggregate Risk................................................................................................... 21
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 3 of 36

7.2 Short-Term Aggregate Risk........................................................................................ 21

7.3 Intermediate-Term Aggregate Risk ........................................................................... 22

7.4 Chronic Aggregate Risk .............................................................................................. 22

7.5 Cancer Aggregate Risk ................................................................................................ 22

8.0 Cumulative Exposure/Risk Characterization ..................................................................22

9.0 Occupational Exposure/Risk Characterization ...............................................................23

9.1 Short- and Intermediate-Term Handler Risk ........................................................... 23

9.2 Short- and Intermediate-Term Post-Application Risk............................................. 24

9.2.1 Dermal Post-Application Risk ............................................................................. 24

9.2.2 Restricted Entry Interval ..................................................................................... 25

9.2.3 Inhalation Post-Application Risk ........................................................................ 25

10.0 References............................................................................................................................25

Appendix A. Toxicology Profile and Executive Summaries...................................................27

A.1 Toxicology Data Requirements................................................................................... 27

A.2 Toxicity Profile of Trifloxystrobin Technical............................................................ 28

Appendix B. Physical/Chemical Properties.............................................................................32

Appendix C. Review of Human Research ................................................................................32

Appendix D. International Residue Limit Status....................................................................33

Appendix E. Residential and Occupational Exposure/Risk Summary Table ......................34
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 4 of 36

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#3F8164, Bayer CropScience (Bayer) has submitted a label amendment to add chickpea, 

dry peas, and lentils to the label for USF 0728 325 SC Fungicide (EPA Reg. No. 264-1055), thus 

petitioning for the associated tolerances. USF 0728 325 SC Fungicide, henceforth referred to as 

USF, is a suspension concentrate (SC) formulation containing 13.7% active ingredient (ai) by

weight (1.27 lb ai/gal). Although USF is a mixed active ingredient (MAI) product also 

containing 16.0% prothioconazole (1.49 lb prothioconazole per gallon), this document only

addresses the human health effects of trifloxystrobin. The proposed use of prothioconazole will 

be evaluated in a separate document.

Since the last risk assessment, the 28-day dermal study in rats has been reclassified as showing 

no adverse systemic effects up to the limit dose of 1,000 mg/kg/day because the observed 

increases in liver and kidney weights were not accompanied with any histopathological 

correlates and not considered adverse. Thus, a dermal point of departure (POD) is no longer 

relevant for human health risk assessment.

Proposed Use Profile

USF 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 chickpea, dry peas, and lentils, is 12.0 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 

10- to 14-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. Exposures via diet and drinking water are expected for all 

durations; residential handler and post-application 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. The primary target organ of toxicity is 

the liver in dogs, mice, and rats in subchronic and chronic studies. 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. The requirement for 

a subchronic neurotoxicity study has been waived (TXR0056150, D. Smegal, 01/05/2012), and

the requirement for a subchronic inhalation study has also been waived (TXR0056957, U. 

Habiba, 05/22/2014). Trifloxystrobin exhibits low acute mammalian toxicity via oral (Toxicity

Category IV), dermal (Toxicity Category IV), and inhalation (Toxicity Category IV) routes of 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 5 of 36

exposure. Trifloxystrobin is a mild eye and skin irritant, and is a strong dermal sensitizer. 

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 assumed tolerance level residues and 

100% crop treated (%CT) for all commodities, and were not of concern. 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. The acute dietary (food + drinking water) risk estimate for females 

13-49 years old is 1.3% of the acute population adjusted dose (aPAD) at the 95th percentile. The 

chronic dietary (food + drinking water) risk estimates represented 32% of the chronic population 

adjusted dose (cPAD) for the general U.S. population and 78% 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 have been reassessed to reflect updates to HED’s 2012 Residential 

Standard Operating Procedures (SOPs) along with changes in dermal risk assessment hazard 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) range from 8,100 to 170,000,000. Short-term 

post-application 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 children) and incidental 

oral (only children 1 to <2 years). For adults, females age 13-49 years old, and children 1 to <2 

years old, the short-term aggregate risk estimates are not of concern; the MOEs are 300, 300, and 

120, respectively.

Occupational Handler Exposures and Risk Estimates

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

intermediate-term inhalation risk estimates are not of concern without personal protective 

equipment (PPE). Short- and intermediate-term inhalation MOEs range from 6,600 to 150,000. 

Note that only engineering control (enclosed cockpit) data are available to assess risks to

handlers operating aircrafts.

Occupational Post-Application Exposures and Risk Estimates

An occupational post-application dermal exposure and risk assessment was not conducted 

because an adverse systemic dermal hazard was not identified for trifloxystrobin. Based on the 

Agency's current practices, a quantitative non-cancer occupational post-application inhalation 

exposure assessment was not performed for trifloxystrobin at this time. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for trifloxystrobin. The 12-hour restricted entry
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 6 of 36

interval (REI) listed on the label is adequate to protect agricultural workers from post-application 

exposures to trifloxystrobin.

Dermal Sensitizer Worker Notification Label Recommendation

According to 40 CFR 156.210 (b), any product that is a dermal sensitizer should bear the 

following statement on the label: “Notify workers of the application by warning them orally and 

by posting warning signs at entrances to treated areas.”

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).

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 on chickpea, dry peas, and lentils, 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 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 7 of 36

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 recommended tolerances and 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)

Pea, dry, seed 0.06 0.06

Pea, dry, hay 15 15 Pea, field, hay

Pea, dry, vines 4 4 Pea, field, vines

Chickpea, seed 0.06 Not Needed

Covered by pea, dry, seed. 

Increase tolerance to harmonize 

with Canada.

Chickpea, hay 15 Not Needed

Chickpea, vines 4 Not Needed

Lentil, seed 0.06 Not Needed Covered by pea, dry, seed.

2.2.3 Revisions to Petitioned-For Tolerances

Tolerances for chickpea hay and vines are not needed since both commodities are not significant 

livestock feed items. The proposed pea, dry, hay and pea, dry, vines commodity definitions need 

to be revised to pea, field, hay and pea, field, vines to reflect the correct commodity definitions. 

The proposed tolerances on chickpea seed and lentil seed are not needed since pea, dry, seed 

includes these commodities. Based on the Organization for Economic Cooperation and 

Development (OECD) tolerance calculation spreadsheet, the proposed tolerance for chickpea, 

seed is 0.04 ppm. However, a tolerance of 0.06 ppm is recommended for harmonization 

purposes.

2.2.4 International Harmonization

Codex MRLs are expressed in terms of trifloxystrobin for plants; thus, harmonization of MRLs 

is not possible. The Codex residue definition for livestock is the same as the US. The Canadian 

residue definitions for plants and livestock are the same as the US. There are no Codex MRLs 

established on the proposed crops. Canadian MRLs exist for dry chickpea, dry field peas, and 

dry lentils at 0.02 ppm. This petition is reviewed as a workshare with Canada, and tolerances for 

the proposed crops are harmonized. The International Residue Limit Status is detailed in

Appendix D.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 8 of 36

2.2.5 Label Recommendation

According to 40 CFR 156.210 (b), any product that is a dermal sensitizer should bear the 

following statement on the label: “Notify workers of the application by warning them orally and 

by posting warning signs at entrances to treated areas.”

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, including corn and soybean. It is a

strobilurin-class fungicide (also termed methoxyacrylates) 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. In PP#3F8164, Bayer has 

submitted a label amendment to add chickpea, dry peas, and lentils to the label for USF (EPA 

Reg. No. 264-1055), thus petitioning for the associated tolerances. USF is an SC formulation 

containing 13.7% ai by weight (1.27 lb ai/gal).

3.1 Chemical Identity

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) Trifloxystrobin/ Prothioconazole USF 0728 325 SC Fungicide; 1.27 lb ai/gal 

trifloxystrobin and 1.49 lb ai/gal prothioconazole; EPA Reg. No. 264-1055

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

O

N

CF3

N

O

O

CH3

O

H C3

CH3

O

N

CF3

N

OH

O O

H3C

CH3
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 9 of 36

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 USF (EPA Reg. No. 264-1055). The newly proposed 

use pattern is presented in Table 3.3.

Table 3.3. Summary of Proposed Use Directions for USF 0728 325 SC Fungicide (EPA Reg. No. 264-1055)

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

Chickpea, Dry Peas, and Lentils

c

Broadcast 

Foliar: 

ground, aerial, 

chemigation, or 

handheld

12 fl oz

product/A

0.12 lb ai/A

0.012 lb 

ai/gald

2

24 fl oz 

product/A

0.24 lb ai/A

7 for 

Forage

30 for 

Seed

Begin fungicide applications 

preventatively and continue as needed on 

a 10- to 14-day interval. Use the shorter 

interval when conditions are favorable for 

severe disease pressure.

a SC = suspension concentrate.

b PHI = pre-harvest interval.

c EPA Reg. No. 264-1055 is a mixed active ingredient (MAI) also containing 16% prothioconazole by weight (1.49 

lb prothioconazole per gallon).

d 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.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 10 of 36

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 

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) is 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% in the bile of male and female rats, 

respectively. With high dose administration, the absorption was 41% and 27%, with 35% and 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 11 of 36

19% 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 LOAEL of 337 mg/kg/day 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 by

current criteria, the increased liver weights were not considered to be adverse because they were 

minimal and not confirmed by histopathological correlates. Therefore, the NOAEL for this 

dermal subchronic study was set at 1000 mg/kg/day and the LOAEL was not established, which 

invalidated the comparison with the 28-day oral range-finding study and the calculated dermal 

absorption factor.

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. However, in 

the absence of actual data on trifloxystrobin, a DAF of 100% is used for risk assessment.

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 increase in incidences 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 lowest observed adverse effect level (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 Human Health Risk Assessment DP No. D413109

Page 12 of 36

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.

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 completed 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 reproduction 

(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.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 13 of 36

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% crop treated (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. These data are reliable and are not expected to underestimate 

risk to adults or children. The Residential SOPs are based upon reasonable “worst-case” 

assumptions and are not expected to underestimate risk.

4.5 Toxicity Endpoint and Point of Departure Selection

As discussed in Section 4.2, in the absence of dermal absorption data on trifloxystrobin a dermal 

absorption factor of 100% is assumed for this risk assessment. Since no dermal or systemic 

toxicity was observed in the available 28-day dermal subchronic study up to 1000 mg/kg/day

(the limit dose), a dermal hazard has not been identified for risk assessment for the general 

population, including children.

The 28-day dermal subchronic study did not assess the potential for developmental toxicity after 

dermal exposure. However, there is no concern for fused sternebrae noted in rabbit fetuses at 

250 mg/kg/day in a developmental toxicity study, because these effects occurred only at 

maternally toxic dose levels (maternal LOAEL = 50 mg/kg/day) and there are no susceptibility

issues. Therefore, a dermal hazard has not been identified for risk assessment for women of 

child-bearing age.

4.5.1 Recommendation for Combining Routes of Exposure for Risk Assessment

When common toxicity endpoints are selected for the dermal, oral, and inhalation routes of 

exposure they may be combined together. For short-, intermediate-, and long-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.

4.5.2 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.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 14 of 36

4.5.3 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 4.5.3.

Table 4.5.3. 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 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.

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 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.

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
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 15 of 36

Table 4.5.3. 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

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 

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
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 16 of 36

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

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 dry peas, 

chickpeas, and lentils (DP413711, M. Negussie, 05/18/2014). The trials reflect the proposed use 

pattern and the number and locations of the trials are acceptable based on the ChemSAC minutes 

of 20 March, 2013. Adequate storage stability data are available to support the storage durations 

and conditions of samples of dry pea commodities, chickpeas, and lentils 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 use on dry peas does 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 plantback 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.

In addition to evaluating the EDWCs from the proposed use, EDWCs were reevaluated for all 

existing uses with the Pesticide Root Zone Model for Ground Water (PRZM-GW),

1 which 

models continued use of trifloxystrobin over many years (DP413801, M. Biscoe, 01/28/2014). 

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 

 

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. D413109

Page 17 of 36

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).

An acute dietary assessment was conducted assuming tolerance level residues and 100% crop 

treated (%CT) for all commodities. DEEM version 7.81 default processing factors were 

assumed except for where tolerances were established for processed commodities. For the 

dietary assessment, a value of 0.20 ppm for the metabolite L7a was added to the tolerance level 

for liver; 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, 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 CGA321113 declined in/on strawberries after washing and cooking. The default processing factor of 

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

acute assessment.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 18 of 36

A chronic dietary (food and drinking water) exposure and risk assessment was conducted

assuming 100% crop treated, tolerance level residues and anticipated residues (ARs) for grapes, 

apples, oranges, and pears. For the dietary assessment, a value of 0.20 ppm for the metabolite 

L7a was added to the tolerance level for liver. DEEM version 7.81 default processing factors 

were assumed except for where tolerances were established for processed commodities. 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. 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. The dietary exposure for food and 

water at the 95th percentile of exposure distribution is estimated at 1.3% 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 water is estimated at 32% of the cPAD for the general U.S. 

population and 78% 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

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

0.012139 32

All Infants (< 1 year old) 0.029751 78

Children 1-2 years old 0.026545 70

Children 3-5 years old 0.020721 54

Children 6-12 years old 0.012755 34

Youth 13-19 years old 0.008879 23
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 19 of 36

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

Adults 20-49 years old 0.011282 30

Adults 50-99 years old 0.010870 29

Females 13-49 years old 0.032259 1.3 0.010893 29

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 reassessed in this document to reflect updates to HED’s 2012 

Residential SOPs along with changes in dermal risk assessment hazard and changes in the policy

for body weight assumptions (DP413713, N. Tsaur, 05/15/2014). The revision of residential 

exposures does impact the human health aggregate risk assessment for trifloxystrobin.

There are various formulations registered for residential use on turfgrass and ornamentals, which 

include water dispersible granules (WG), water soluble packaging (WSP), granules (G), and 

liquid (L). The currently registered end-use products (EPs) available for residential use include:

1. CompassTM Fungicide (EPA Reg. No. 432-1371), a WG formulation (Restricted Use),

2. ArmadaTM 50 WP (EPA Reg. No. 432-1412), a WSP formulation,

3. CompassTM G Fungicide (EPA Reg. No. 432-1432), a G formulation,

4. TartanTM Fungicide (EPA Reg. No. 432-1446), an L formulation,

5. Chipco® 26019T Fungicide (EPA Reg. No. 432-1505), an L formulation, and

6. ArmadaTM 50 WDG (EPA Reg. No. 432-1513), a WG formulation.

Bayer Environmental Science (Bayer) is the registrant of all six products. Two of the labels 

(CompassTM Fungicide and CompassTM G Fungicide) are restricted to professional handlers only. 

However, the use of both products on residential and recreational turf may still result in 

residential post-application exposure. Furthermore, there are no granular or liquid formulation 

uses on ornamentals (only WSP and WG are registered for use on residential ornamentals).

The reassessment of all registered residential products do 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. 

Appendix E summarizes all assessed residential exposure and risk estimates.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 20 of 36

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 

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

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

assessment was not performed for trifloxystrobin at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), low vapor pressure (3.4×10-6Pa, or 2.55×10-7 mm Hg 

at 25oC) and the low proposed use rate (0.12 lb ai/A). However, volatilization of pesticides may

be a source of post-application inhalation exposure to individuals nearby pesticide applications. 

The Agency sought expert advice and input on issues related to volatilization of pesticides from 

its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 20102. The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are developed, the 

 

2 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 21 of 36

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for trifloxystrobin.

6.4 Spray Drift

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 

other parties to develop the best spray drift management practices (see the Agency’s Spray Drift 

website for more information). 3 The Agency is also taking means to qualitatively and 

qualitatively address spray drift as a potential source of exposure in risk assessments for 

pesticides through existing programs such as Ag Drift and chemical specific properties of 

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.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) 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 

 

3 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 22 of 36

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.

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 0.012139 0.00047 NAf0.012609 300

Children

1-2 years old

(Oral Exposure)

3.8 100 0.026545 NAf0.0052 0.031745 120

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 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 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 23 of 36

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 

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

Occupational handler and post-application exposure may occur by the dermal and inhalation 

routes of exposure only. For short- and intermediate-term exposure, only inhalation exposures 

were assessed since there is no systemic hazard from the dermal route of exposure. The results 

of the occupational handler exposure and risk assessment indicate that short- and intermediateterm risk estimates are not of concern (DP416655, N. Tsaur, 03/27/2014). Appendix E

summarizes all assessed occupational exposure and risk estimates.

9.1 Short- and Intermediate-Term Handler Risk

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

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

agricultural uses. The quantitative exposure/risk assessment developed for occupational handlers 

is based on several scenarios which include mixing/loading/applying the SC formulation of 

trifloxystrobin. Methods of application include aerial, chemigation, groundboom, and handheld 

equipment. Flagging for aerial use is also a potential source of worker exposure.

HED classifies exposures from 1 to 30 days as short-term and exposures from 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 onemonth 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). The area treated or amount handled is based on HED 

ExpoSAC Policy No. 9.1 (refer to Appendix E for these assumptions for each scenario). Since 

the PODs for short- and intermediate-term exposure are the same, the short-term assumptions 

and risk calculations are protective of both durations.

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 the 

Pesticide Handlers Exposure Database (PHED) 1.1, the Agricultural Handlers Exposure Task 

Force (AHETF) database, or other registrant-submitted occupational exposure studies. Some of 

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

Federal Insecticide, Fungicide, and Rodenticide Act (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 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 24 of 36

Reference Table4”, which, along with additional information on HED policy on use of surrogate 

data, including descriptions of the various sources, can be found at the Agency website5.

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

intermediate-term inhalation risk estimates are not of concern (i.e. all MOEs ≥ 100) at baseline 

mitigation (no PPE). Since the short- and intermediate-term PODs are the same, the inhalation 

MOEs are also the same, ranging 6,600 to 150,000. Note that only engineering control (enclosed 

cockpit) data are available to assess risks to handlers operating aircrafts.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for 

exposure to pilots in enclosed cockpits. Therefore, risks to pilots are assessed using the 

engineering control (enclosed cockpits) and baseline attire (long-sleeve shirt, long pants, shoes, 

and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, 

pilots are not required to wear protective gloves for the duration of the application. With this 

level of protection, there are no risk estimates of concern for applicators.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers where appropriate, agricultural aviation has changed dramatically over the past 

two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of 

their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily 

from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide 

applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent 

(2012) NAAA survey. The Agency will continue to monitor all available information sources to 

best assess and characterize the exposure potential for human flaggers in agricultural aerial 

applications.

9.2 Short- and Intermediate-Term Post-Application Risk

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.

9.2.1 Dermal Post-Application Risk

There is potential for short- and intermediate-term occupational exposure during post-application 

activities. However, there is no adverse systemic dermal hazard for any exposure duration for

trifloxystrobin. 

 

4 Available: http://www.epa.gov/opp00001/science/handler-exposure-table.pdf

5 Available: http://www.epa.gov/pesticides/science/handler-exposure-data.html
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 25 of 36

9.2.2 Restricted Entry Interval

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.

9.2.3 Inhalation Post-Application Risk

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

assessment was not performed for trifloxystrobin at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), low vapor pressure (3.4×10-6Pa, or 2.55×10-7 mm Hg 

at 25oC) and the low proposed use rate (0.12 lb ai/A). 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, 20106. The Agency is in the process of evaluating 

the SAP report as well as available post-application inhalation exposure data generated by the 

ARTF and may, as appropriate, develop policies and procedures to identify the need for, and 

subsequently, the way to incorporate occupational post-application inhalation exposure into the 

Agency's risk assessments. If new policies or procedures are put into place, the Agency may

revisit the need for a quantitative occupational post-application inhalation exposure assessment 

for trifloxystrobin.

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.

10.0 References

Biscoe, Melanie. 01/28/2014. DP Barcode 413801. “Trifloxystrobin: Drinking Water Exposure 

Assessment in Support of a Proposed New Use on Dry Peas, Chickpeas, and Lentils (Reg. 

Nos. 264-776 (technical) and 264-1055).”

Negussie, Meheret. 03/18/2014. DP Barcode 413711. “Trifloxystrobin. Application for Section 

3 Registration for Uses on Dry Peas, Chickpeas, and Lentils. Summary of Analytical 

Chemistry and Residue Data.”

 

6 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 26 of 36

Negussie, Meheret. 04/14/2014. DP Barcode 413712. “Trifloxystrobin. Acute and Chronic 

Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for Uses on 

Dry Peas, Chickpeas, and Lentils.”

Habiba, Uma. 05/22/2014. TXR Number 0056957. “Trifloxystrobin. Summary of Hazard and 

Science Policy Council (HASPOC) Meeting on April 24, 2014: Recommendation on the 

Waiver Request for a 28-day Inhalation Study.”

Tsaur, Nancy. 05/14/2014. 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. D413109

Page 27 of 36

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. D413109

Page 28 of 36

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. D413109

Page 29 of 36

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. The observed increases in liver 

and kidney weights 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 nondose 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. 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 30 of 36

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

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

870.5100

In vitro bacterial 

reverse gene 

mutation -

Salmonella

44496712

44496715 

44496716

44496717

Acceptable/Guideline

Negative

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. 
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 31 of 36

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

Guideline No. Study Type MRID No. (year)/ 

Classification /Doses Results

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. D413109

Page 32 of 36

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 10-6Pa, 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 PHED and

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. D413109

Page 33 of 36

Appendix D. International Residue Limit Status

Table D.1. Trifloxystrobin Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition

US Canada Mexicob Codex

40 CFR 180.555:

Plants and Livestock: sum of 

trifloxystrobin, benzeneacetic acid, (E,E)-α-

(methoxyimino)-2-[[[[1-[3-(trifluoromethyl) 

phenyl]ethylidene] amino]oxy]methyl]-, 

methyl ester, and the free form of its acid 

metabolite CGA–321113, 

(E,E)-methoxyimino-[2-[1-(3-

trifluoromethyl-phenyl)-

ethylideneaminooxymethyl]-phenyl]acetic 

acid, calculated as the stoichiometric 

equivalent of trifloxystrobin

Methyl (α,E)-α-

(methoxyimino)-2-[[[(E)-

[1-[3-

(trifluoromethyl)phenyl]eth

ylidene]amino]oxy]methyl]

benzeneacetate, including 

the metabolite (α,E)-α-

(methyoxyimino)-2-[[[(E)-

[1-[3-

(trifluromethyl)phenyl]ethy

lidene]amino]oxy]methyl]b

enzeneacetic acid, 

expressed as trifloxystrobin

Plant: Trifloxystrobin

Livestock: sum of 

trifloxystrobin and 

[(E,E)-methoxyimino-

{2-[1-(3-

trifluoromethylphenyl)

ethylideneaminooxym

ethyl]

phenyl}acetic acid] 

(CGA 321113), 

expressed as 

trifloxystrobin. The 

residue is fat-soluble.

Commoditya

Tolerance/Maximum Residue Limit

US Canada Mexicob Codex

ppm mg/kg

Pea, dry, seed 0.06

0.06

(proposed) 

(pea field, 

pea pigeon, 

chickpea, 

lentil) seed

0.02 dry 

(field peas, 

chickpeas, 

lentils)

Pea, field, hay 15

Pea, field, vines 3

Completed: M. Negussie; 02/25/2014

a Includes only commodities of interest for this action.

b Mexico adopts US tolerances and/or Codex MRLs for its export purposes.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 34 of 36

Appendix E. Residential and Occupational Exposure/Risk Summary Table

Table E.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. D413109

Page 35 of 36

Table E.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 E.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.
TRIFLOXYSTROBIN Human Health Risk Assessment DP No. D413109

Page 36 of 36

Table E.3. Occupational Handler Exposure and Risk Estimates for Trifloxystrobin Use on Typical Field 

Cropsa

Exposure Scenario

Inhalation 

Unit 

Exposureb

Maximum

Application 

Ratec

Area Treated or 

Amount Handled 

Dailyd

Inhalation 

Dosee Inhalation MOEf

μg/lb ai lb ai/A Acres mg/kg/day ST/IT LOC = 100

Mixer/Loader

Mixing/Loading Dry Flowables for 

Aerial and Chemigation Application 0.219

0.12 350 0.000114 33,000

Mixing/Loading Dry Flowables for 

Groundboom Application 0.12 80 0.0000261 150,000

Applicator

Applying Sprays for Aerial 

Application 0.068 0.12 350 0.0000354 110,000

Applying Sprays for Groundboom 

Application 0.34 0.12 80 0.0000405 94,000

Flagger

Flagging for Aerial Application 0.35 0.12 350 0.000183 21,000

Mixer/Loader/Applicator

M/L/A Dry Flowables for 

Mechanically-Pressurized Handgun 

Sprayers

3.9 0.012

lb ai/gal

1000

gallons 0.00058 6,600

a “Typical Field Crops” include chickpea, dry peas, and lentils.

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

Baseline (no respirator) except for aerial applicator which includes engineering controls.

c Based on the maximum application rates on the proposed labels (Reg. No. 264-1055, USF 0728 325 SC Fungicide).

d Exposure Science Advisory Council Policy #9.1.

e Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or 

gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (80 kg).

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