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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Shaunta Hill (703) 347-8961

Syngenta Crop Protection LLC. PP#

EPA has received a pesticide petition PP# 2F8121 from Syngenta Crop 

Protection LLC., P.O. Box 18300, Greensboro, NC 27419-8300 proposing, 

pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act 

(FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.

1. by establishing a tolerance for residues of Benzovindiflupyr in or on the 

raw agricultural commodity [Apple, wet pomace]insert] at [0.6] parts per 

million (ppm), [barley, grain] at [1.5] ppm, [barley, hay] at [15] ppm, [barley, 

straw] at [15] ppm, [corn, field, grain] at [0.02] ppm, [corn, field, forage] at [3] 

ppm, [corn, field, stover] at [15] ppm [corn, pop, grain] at [0.02] ppm, [corn, 

pop, stover] at [15] ppm, [corn, sweet, ear] at [0.01] ppm, [corn, sweet, forage]

at [4] ppm, [corn, sweet, stover] at [5] ppm, [cottonseed, subgroup 20C] at 

[0.15] ppm, [cotton, grin byprouducts] at [3] ppm, [vegetables, cucurbit, crop 

group 9] at [0.2] ppm,. [fruits, pome, crop group 11-10] at [0.2] ppm, [fruits, 

small vines climbing, except fuzzy kiwi subgroup 13-07F] at [1] ppm, [grain, 

aspirated fractions] at [7] ppm, [oat, grain] at [1.5] ppm, [oat, hay] at [15] ppm, 

[oat, straw] at [15] ppm, [peas and bean, dried shelled, except soybean, 

subgroup 6C] at [0.2] ppm [peas, hay] at [7] ppm, [peas, vine] at [1.5] ppm,

[peanut, nutmeat] at [0.01] ppm, [peanut, hay] at [15] ppm, [potato, wet peel]

at [0.1] ppm, [raisin] at [4] ppm, [rapeseed, subgroup 20A] at [0.15] ppm, [rye, 

grain] at [0.1] ppm, [rye, hay] at [15] ppm,.[rye, straw] at [10] ppm, [soybean, 

seed] at [0.07] ppm, [soybean , forage] at [15] ppm,. [soybean, hay] at [50] 

ppm, [vegetables, fruiting, crop group 8-10] at [0.8] ppm, [vegetables,

tuberous and corm subgroup 1C] at [0.02] ppm, [wheat, grain] at [0.1] ppm,

[wheat, forage] at [4] ppm, [wheat, hay] at [15] ppm,[wheat, straw] at [10] 

ppm; and in or on the following animal commodities [cattle, fat] at [0.01] ppm, 

[cattle, kidney] at [0.01] ppm,[cattle, liver] at [0.01] ppm, [cattle, meat] at [0.01] 

ppm, [cattle, byproducts] at [0.01] ppm; [egg] at [0.01] ppm; [goat, fat] at 

[0.01] ppm,[goat, kidney] at [0.01] ppm, [goat, liver] at [0.01] ppm, [goat, meat]

at [0.01] ppm, [goat, meat byproducts] at [0.01] ppm; ; [hog, fat] at [0.01] ppm; 

[hog, liver] at [0.01] ppm,[hog, meat] at [0.01] ppm, [hog, meat byproducts] at 

[0.01] ppm, [horse, fat] at [0.01] ppm, [horse, kidney] at [0.01] ppm, [horse, 

liver] at [0.01] ppm, [horse, meat] at [0.01] ppm,[horse, meat byproducts] at 

[0.01] ppm; [milk] at [0.01] ppm, [milk, fat] at [0.01] ppm; [egg] at [0.01] ppm; 

[poultry, byproducts] at [0.01] ppm, [poultry, fat] at [0.01] ppm, [poultry, liver]
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at [0.01] ppm, [poultry, meat] at [0.01] ppm, [poultry, skin] at [0.01] ppm,

[sheep, fat] at [0.01] ppm, [sheep, kidney] at [0.01] ppm, [sheep, liver] at 

[0.01], [sheep, meat] at [0.01] ppm, [sheep, meat byproduct] at [0.01] ppm. 

EPA has determined that the petition contains data or information regarding 

the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not 

fully evaluated the sufficiency of the submitted data at this time or whether the 

data supports granting of the petition. Additional data may be needed before 

EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. [Plant Metabolism studies with benzovindiflupyr

(SYN545192) were performed in wheat, soybean and tomatoes as representative 

crops in order to characterize the fate of benzovindiflypur in all crops. Two

radiocarbon labels were studied in each crops, with 14-C labels positioned in 

phenyl and pyrazole ring structures. Benzovindiflupyr was the predominant 

component of residue in most crops. The metabolism in all plants (soybean, 

wheat, tomatoes) was very similar. In all crops, the main path was via oxidative

metabolism of alicyclic system, N-demethylation of pyrazole ring, conjugation of 

hydroxylated parent and cleavage between phenyl and pyrazole ring. There 

was, however, some variation on the extent and nature of conjugations between 

crops.]

2. Analytical method. [The proposed definition of the residue for 

benzovindiflupyr (SYN545192) in commodities of plant origin is parent 

SYN545192 for both compliance monitoring and consumer risk assessments. 

The corresponding definitions in commodities of animal origin are parent 

SYN545192 for monitoring and sum of SYN545192 and SYN546039 for risk 

assessment. Both Method GRM042.03A and GRM042.04A for plant products 

have been developed determine parent SYN545192 and its metabolite 

SYN546039 (and conjugates) with a limit of quantification (LOQ) of 0.01 mg/kg 

for both analytes. GRM042.04A also determines metabolite SYN545720 with an 

LOQ of 0.01 mg/kg. Method GRM042.08A has been developed for the 

determination of SYN545192 and its metabolites SYN546039 and SYN546206 in 

rotational crops, with an LOQ of 0.01 mg/kg for all three analytes. Method 

GRM042.06A (also known as Charles River Method No. 1887 Version 2.0) for 

animal products has been validated for use in pre-registration development 

studies. The method determines parent SYN545192 and its metabolites 

SYN546039 and SYN546422, with an LOQ of 0.01 mg/kg for each analyte. 

Method GRM023.03A was used to analyse residues of SYN545720 in the 

storage stability study demonstrating the storage stability of SYN545720 residues 

in a range of commodities under frozen conditions.]

3. Magnitude of residues. [Field trials were carried out to determine the 

magnitude of residue in/on pome fruit (crop group 11-10), small cereal grains

(wheat, barley), corn, cotton, cucurbits (crop group 9), dried shelled peas and 

bean except soybean (subgroup 6C), fruiting vegetables (crop group 8-10), grape 
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(subgroup 13-07F), peanuts, canola (rapeseed) subgroup 20A, soybean, and 

tuberous and corm subgroup 1C. The number and locations of the field trials are

in accordance with OPPTS 860.1500. Field trials were carried out using the 

maximum label rates, maximum number of applications, and the minimum preharvest interval (PHI) for all the crops. Additional trials have been conducted in 

Canada as supporting data to get registration in Canada and propose 

harmonized tolerances between US and Canada. Detected residues of 

benzovindiflupy in all crops support the propsed tolerances based on parent 

only.]

B. Toxicological Profile

1. Acute toxicity. [The estimated acute medical lethal dose (MLD) for 

benzovindiflupyr (SYN545192) via the oral route was 55 mg/kg. The median 

lethal concentration (MLC) following acute inhalation exposure was estimated to 

be greater than 0.56 mg/l. The acute dermal MLD was shown to be greater 2000 

mg/kg. SYN545192 was only mildly irritating to the skin and moderately irritating 

to the eyes. The acute toxicity studies place technical benzovindiflupyr in toxicity 

category II for oral and category III for dermal and inhalation. Benzovindiflupyr is 

not a dermal sensitizer.]

2. Genotoxicty. [Benzovindiflupyr (SYN545192) has been examined in a 

range of in vitro and in vivo genotoxicity assays, including endpoints of bacterial 

and mammalian gene mutation and chromosomal damage. In vitro, SYN545192 

was negative for gene mutation in bacterial (Ames test) and mammalian cells 

(L5178Y TK+/- mouse lymphoma). The L5178Y TK+/-assay, which is also able to 

detect chromosomal damage by assessment of colony sizes (small and large 

colony sizes are associated with clastogenic or mutagenic effects respectively), 

was also negative for clastogenicity. In the in vitro cytogenetic assay using 

primary human lymphocyte cultures, SYN545192 did not induce any treatmentrelated chromosomal aberrations. In vivo, SYN545192 was found to be nonclastogenic in the rat bone marrow micronucleus assay and did not induce 

micronuclei in bone marrow cells.]

3. Reproductive and developmental toxicity. [Benzovindiflupyr

(SYN545192) was evaluated for potential to cause effects on reproductive and 

developmental toxicity in a multi-generation reproductive toxicity study in the rat 

and in pre-natal developmental toxicity studies in the rat and rabbit. 

 Reproductive toxicity: SYN545192 was evaluated in a two-generation 

reproduction study in the rat at dietary inclusion levels of 0, 25, 100, 250 ppm 

(females) or 600 ppm (males).

The parental NOAEL was considered to be 100 ppm (equivalent to 6.8 

mg/kg/day for P generation males during pre-pairing). The NOEL for 

reproduction was 600 ppm in males (equivalent to 40.5 mg/kg/day for P 

generation males during pre-pairing) and 250 ppm in females (equivalent to 19.4 

mg/kg/day for P generation females during pre-pairing). The offspring NOEL for 

general toxic effects was 100 ppm (equivalent to 7.8 mg/kg/day for F1 generation 
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males during pre-pairing). 

 Developmental Toxicity: In a developmental study in the rat, 

SYN545192 was administered at dose levels of 0, 7.5, 15 and 30 mg/kg/day. All 

female animals survived until the scheduled necropsy. Marked clinical signs of 

toxicity (ataxia, hunched posture, prostrate, decreased activity and ruffled fur) 

were observed at 30 mg/kg/day. Mean food consumption, body weight and body 

weight gain were lower at 30 mg/kg/day. Mean foetal body weight was lower at 

30 mg/kg/day and there was a slight delay in ossification which was considered 

to be related to the treatment with the test item and secondary to maternal 

toxicity. The NOEL for maternal and developmental toxicity was 15 mg/kg/day.

In a rabbit dose-range finding study, a dose level of 100 mg/kg/day produced 

severe body weight loss and reduced food consumption that resulted in the early 

termination of all females at this dose level. Excessive body weight losses and 

reduced food consumption also led to abortion and moribundity in individual 

females at 50 mg/kg/day indicating that this dose level was unsuitably high for a 

full developmental toxicity study. On this basis, dose levels of 0, 10, 20, and 35 

mg/kg/day were selected for the definitive prenatal development toxicity study the 

rabbit. 

There were no treatment-related effects on the dams at any dose level. Marginal

effects on maternal body weight gain were seen at 20 and 35 mg/kg/day during 

gestation days 13-20. There were no effects on development. The NOEL for 

maternal and developmental toxicity was 35 mg/kg/day.]

4. Subchronic toxicity. [The short term toxicity of benzovindiflupyr has 

been evaluated by the oral route of administration in rats, mice and dog. In 

addition, dermal toxicity was evaluated in rates in a 28-day study.

Dietary administration of SYN545192 to rats for at least 90 days was associated 

with in-life effects (reduced body weights, food consumption and food utilisation) 

at 750 ppm and above. Covariant liver weights were statistically higher in male 

animals treated at 1500 ppm and in females at 750 ppm. Centrilobular 

hepatocyte hypertrophy of the liver was noted at doses of 750 ppm and above in 

males and at 1500 ppm in females. The NOEL was considered to be 100 ppm for 

both males and females equating to an average of 7.6 mg/kg/day in males and 

8.2 mg/kg/day in females.

Dietary administration of SYN545192 to mice at doses, 0, 100, 300 or 300 ppm 

for a period of at least 91 days was associated with significant initial body weight 

losses resulting in termination of two animals in the toxicokinetic satellite group at 

500 ppm. The NOEL for this study was considered to be 100 ppm for both sexes, 

equating to an average compound intake of 17.0 mg/kg/day in males and 20.9 

mg/kg/day in females. The NOEL is based on the occurrence of mortality in two 

animals at 500 ppm, initial body weight loss, decrease in body weight gain, an 

increased incidence of soft faeces in males, 
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In a 28-day dermal toxicity in rats, no treatment-related effects were observed at 

any dose level up to the limit dose of 1000 mg/kg..]

5. Chronic toxicity. [Benzovindiflupre (SYN545192) has been evaluated for 

chronic toxicity in the rat and for carcinogenic potential in the rat and the mouse. 

In a 2 year combined chronic toxicity/carcinogenicity study in rats, SYN545192 

was tested at dietary inclusion levels conducted at dietary inclusion levels of 0, 

25, 100 and 600 ppm (males) or 400 ppm (females). 

Significantly lower body weight gain, food consumption and food utilisation were 

observed in both sexes at the top dose. ALP, ALT and AST values were 

consistently lower than control values at the top dose. In males at 600 ppm, liver 

weight adjusted for body weight was statistically significantly increased. There 

were no other effects on organ weight. The incidence of centrilobular 

hypertrophy in the liver was statistically significantly higher in top dose males and 

females at 52 and 104 weeks. In males at 600 ppm, the incidence of eosinophilic 

cell foci in the liver was statistically significantly higher after 104 weeks, and a 

higher incidence of hepatocyte vacuolation was seen after 104 weeks. 

A higher incidence of pigmented hepatocytes was observed in females at 400 

ppm after 52 and 104 weeks. In males at 600 ppm, there was a treatment-related 

increase in the incidence of thyroid follicular cell adenomas. There were no other 

treatment-related neoplastic findings. A NOAEL was established at 100 ppm 

(4.88 mg/kg/day in males and 6.66 mg/kg/day in females).

In a carcinogenicity study with SYN545192 (purity 97%), four groups of 50 CD-1 

mice/sex/group were fed diets containing 0, 20, 60 or 200 ppm SYN545192 for at 

least 80 consecutive weeks. The animals well tolerated the administered doses 

up to 8-0 weeks.

The administration of SYN545192 at 200 ppm was associated with a higher 

incidence of simple mucosal hyperplasia in the large intestine (colon and 

caecum) of males and females. There were no effects in the large intestine at 20 

or 60 ppm in either sex. There were no treatment related increases in neoplastic 

findings. 

Based on the findings in this study, a No Observed Effect Level (NOEL) is 

established at 60 ppm, which is equivalent to 7.55 mg/kg/day in males and 8.67 

mg/kg/day in females.]

6. Animal metabolism. [The rat, goat, and hen metabolism studies were 

conducted to determine the nature of the benzovindiflupy residues in animals. 

The rat metabolism study has established that benzovindiflupyr is rapidly 

absorbed by rats following oral administration by gavage. In both poultry and 

goat, the majority of the dosed radioactivity was excreted (mainly in the feces) 

and radioactivity remaining in dietary tissues, milk and eggs was low. In the goat 
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study, milk residues reached plateau residue concentrations (0.035 – 0.046 

mg/kg), after 3 - 4 days dosing. Residues in eggs from the hen study reached 

plateau residue concentrations after approximately 8 days (0.17 – 0.18 mg/kg in 

egg yolk and 0.03 – 0.04 mg/kg in egg white). 

In both species, the highest tissue residues were observed in liver (0.697 – 1.279 

mg/kg in goat and 0.188 – 0.249 mg/kg in hen) and kidney (0.185 – 0.280 mg/kg 

in goat). Residue levels in fat-rich tissues of hen and goat were much lower, 

0.043 mg/kg-0.1 mg/kg. 

There was very little transfer of residues into tissues, milk or eggs following the 

dosing of benzovindiflupyr to the hen or the goat. Metabolic profiles observed in 

livestock commodities arise from just three principle biotransformation.The 

principle routes of metabolism are i) N-pyrazole demethylation of SYN545192 

and ii) oxidation resulting in 

- monohydroxylation of the alicyclic ring,

- alicyclic ring opening of alicyclic monohydroxylated metabolites 

resulting in a dihydroxylated metabolite.

Overall the biotransformation pathway of SYN545192 in ruminants and poultry is 

well understood and consistent with that observed in the rat.]

7. Metabolite toxicology. [SYN546039 (formed via mono hydroxylation on 

the alicyclic ring has been assessed for acute and oral toxicity, in vitro 

genotoxicity (Bacterial reverse mutation). SYN546039 was not acutely toxic by

oral route and was not genotoxic in vitro. These data indicate that SYN546039 is 

of lower toxicity than parent SYN545192 and is not considered to be toxicological 

relevance.

Metabolites NOA449410 and SYN545720 (formed via cleavage between the 

pyrazole and phenyl ring) were also assessed for toxicity. Both metabolites were 

not acutely toxic by oral route, were negative in vitro genotoxicity studies and 

were toxicologically benign up to the limit dose of 1000 mg/kg/day in a 28-day 

and 90-day studies in rat. In rabbit developmental toxicity studies, these 

metabolites were not teratogenic.

Based on these data, metabolites NOA449410 and SYN545720 can be 

characterized as having minimal toxic potential.

8. Endocrine disruption. [Benzovindiflupyr (SYN545192) does not belong

to a class of chemicals known as suspected of having adverse effects on the 

endocrine system. There is no evidence in other relevant toxicity studies (e.g. 

sub-chronic and chronic toxicity, developmental toxicity and multi-generation 

reproductive studies) which would suggest that benzovindiflupyr has any 

endocrine disruptive potential. 

9. Immunotoxicity. [A study was conducted, as specified in US 

OPPTSGuideline 870.7800, to provide information on suppression of the immune 
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system which might occur as a result of repeated exposure to a test chemical. 

Treatment of female CD-1 mice with benzovindflupyr on a continuous basis in the 

diet for a minimum of 28 days resulted in no suppression of the humoral immune 

component of the immune system, based on evaluation of the spleen and thymus 

weights, spleen cell numbers, and the T-cell dependent antibody response of 

splenocytes (antibody forming cell assay). 

The no observed-effect level (NOEL) for the AFC (humoral immune response) 

assay was 400 ppm (equivalent to 97.1 mg/kg of body weight/day), the highest 

dose level evaluated.

C. Aggregate Exposure

1. Dietary exposure. Tier III acute, short-term, intermediate-term, and 

chronic aggregate exposure evaluations were completed for benzovindiflupyr 

(SYN545192) using the Dietary Exposure Evaluation Model software with the 

Food Commodity Intake Database (DEEM-FCID, version 3.15). DEEM-FCID 

software incorporates food consumption data from the National Health and 

Nutrition Examination Survey)/“What We Eat in America” (NHANES/WWEIA) 

dietary survey conducted in 2003-2008. Assessments were conducted for all 

proposed uses on cereals (wheat, barley, oat, rye and triticale), corn, soybean, 

peanuts, cotton, pome fruits (Crop Group 11), grapes (Small Fruits Vine Climbing 

Sub-Group 13-07F except fuzzy kiwi fruit), pulses (dry beans and peas Crop 

Group 6C), potatoes (Tuberous and Corm Subgroup 1C), cucurbits ( crop Group 

9), fruiting vegetables (Crop Group 8), canola (Crop Group 20A), and a proposed 

non-food use on blueberries. Import tolerances were proposed for coffee and 

sugarcane. The definition of the residue for tolerance enforcement and risk 

assessment purposes for crops is parent benzovindiflupyr (SYN545192). The 

assessments utilized residue data from field trials in which benzovindiflupyr was 

applied at the maximum intended use rate and samples were harvested at the 

minimum pre-harvest interval (PHI) to obtain maximum residues. Percent of crop 

treated values were estimated based upon economic, pest, and competitive 

pressures. Secondary residues in animal commodities were estimated based on 

“maximum reasonably balanced diets” and transfer information from feeding 

studies. Drinking water estimates were incorporated directly into the dietary 

exposure assessment using the higher of the estimated drinking water 

concentrations (EDWCs) for surface and ground water. 

i. Food. Acute Exposure. The acute dietary risk assessments were 

performed for all population subgroups with an acute reference dose (aRfD) of 

0.15 mg/kg-bw/day based on an acute no observed adverse effect level (NOAEL) 

of 15 mg/kg/day prenatal developmental toxicity study in rats and an uncertainly 

factor of 100X. The 100X safety factor includes intra- and interspecies 

variations. No additional FQPA safety factor was applied. At the 99.9th%-ile of 

exposures, acute food exposure to the U.S. population resulted in an acute food 

MOE of 14,254 or 0.7% of the aRfD (Benchmark MOE =100; aRfD = 0.15 mg/kg-
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bw/day) of exposures. Acute food exposure to the most sensitive subpopulation 

(children 1 to 2 years old) resulted in an acute food MOE of 5,342 or 1.9% of the 

aRfD (Benchmark MOE =100; 0.15 mg/kg-bw/day). Since the Benchmark MOE 

for this assessment was 100 and since the EPA generally has no concern for 

exposures above the benchmark or below 100% of the aRfD, Syngenta believes 

that there is a reasonable certainty that no harm will result from acute dietary 

(food) exposure to residues arising from the proposed uses for benzovindiflupyr.

Chronic Exposure. The benzovindiflupyr chronic dietary (food only) risk 

assessments were performed for all population subgroups with a chronic 

reference dose of 0.05 mg/kg-bw/day based on a combined 

chronic/carcinogenicity study on rats with no observed adverse effect level 

(NOAEL) of 4.9 mg/kg-bw/day and an uncertainty factor of 100X for intra- and 

inter-species variations. No additional FQPA safety factor was applied. For the 

purpose of the aggregate risk assessment, exposure values were expressed in 

terms of margins of exposure (MOE), which were calculated by dividing the 

NOAEL by the exposures for each population subgroup. In addition, exposures 

were also expressed as percentages of the reference dose (%RfD). Chronic 

(food only) exposure to the U.S. population resulted in a chronic food MOE of 

143,136 (0.1% of the chronic RfD of 0.05 mg/kg-bw/day). The most sensitive 

sub-population was children (1-2 years old) with a chronic food MOE of 58,902 

(0.2% of the chronic RfD). Since the benchmark MOE for this assessment was 

100 and since the EPA has no concern for exposures resulting in an MOE above 

the Benchmark MOE or below 100% of the reference dose, Syngenta believes 

that there is a reasonable certainty that no harm will result from dietary (food 

only) exposure to residues arising from the proposed uses for benzovindiflupyr.

Cancer. Benzovindiflupyr is considered “not likely to be a human carcinogen”. 

Therefore, no cancer risk assessment was performed for benzovindiflupyr.

ii. Drinking water. To determine the Estimated Drinking Water 

Concentrations (EDWCs) for SYN545192 in surface water the Tier 1 model, 

FQPA Index Reservoir Screening Tool (FIRST v1.1.1), was used. For 

groundwater the Tier 1 model, Screening Concentration in Ground Water (SCIGROW v2.3), was used. The maximum field application rate for multiple crops 

including corn, cucurbits, fruiting vegetables, and corm vegetables, and grapes is 

75 g ai/ha/application (0.068 lb. a.i./A/application) x 4 applications/year. A 

minimum 7 day retreatment interval is specified, and after the second application 

a fungicide with a different mode of action must be used. The modeling was 

conducted using environmental fate parameters, in accordance with EPA’s 

guidance, to identify the highest benzovindiflupyr (SYN545192) EDWCs from all 

proposed uses. The predicted EDWCs were corrected with a Percent Cropped 

Area (PCA) adjustment factor of 0.95. FIRST calculated a surface water acute 

EDWC of 6.515 μg/L (ppb) and a chronic EDWC of 1.596 μg/L (ppb). SCIGROW calculated a groundwater EDWC (acute and chronic) of 0.00428 μg/L 

(ppb). Since the surface water EDWCs exceed the ground water EDWC, the 
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surface water values are considered to be protective for any ground water 

concentration concerns. 

Acute Exposure from Drinking Water. The acute surface water EDWC of 6.515 

ppb was input directly into the DEEM-FCIDTM software as “water, direct and 

indirect, all sources” to model the acute drinking water exposures. Exposure 

contributions at the 99.9th%-ile of exposures were determined by taking the 

difference between the aggregate (food + drinking water) exposures and the food 

(alone) exposures for each population subgroup. Acute drinking water exposure 

to the U.S. population resulted in an acute drinking water MOE of 38,265 (0.3% 

of the acute RfD of 0.15 mg/kg-bw/day). The most exposed sub-population was 

infants (<1 year old) with an acute drinking water MOE of 20,107 (0.5% of the 

aRfD of 0.15 mg/kg/day). Since the benchmark MOE for this assessment was 

100 and since the EPA has no concern for exposures resulting in an MOE above 

the Benchmark MOE or below 100% of the reference dose, Syngenta believes 

that there is a reasonable certainty that no harm will result from drinking water 

exposure to residues arising from the proposed uses for benzovindiflupyr.

Chronic Exposure from Drinking Water. The chronic surface water EDWC of 

1.596 ppb was input directly into the DEEM-FCIDTM software as “water, direct 

and indirect, all sources” to model the chronic drinking water exposures. Chronic 

drinking water exposure to the U.S. population resulted in a chronic drinking 

water MOE of 146,624 (0.1% of the chronic RfD of 0.05 mg/kg-bw/day). Chronic 

drinking water exposure to the most exposed sub-population (infants, <1 year 

old) resulted in a chronic drinking water MOE of 56,864 (0.2% of the chronic RfD 

of 0.05 mg/kg-bw/day). Since the benchmark MOE for this assessment was 100 

and since the EPA has no concern for exposures resulting in an MOE above the 

Benchmark MOE or below 100% of the reference dose, Syngenta believes that 

there is a reasonable certainty that no harm will result from drinking exposure to 

residues arising from the proposed uses for benzovindiflupyr.

2. Non-dietary exposure. Non-dietary residential exposure risk 

assessments were performed for use of benzovindiflupyr formulated as an 

emulsifiable concentrate, soluble liquid or wettable granule for residential turf 

including sod farms, golf courses, and sports fields. Residential exposure risk 

assessments were performed for use of benzovindiflupyr formulated as a 

wettable granule for ornamentals grown in greenhouses and outdoor nurseries 

and for vegetable transplants grown for resale to customers. Benzovindiflupyr is 

labeled for professional use only; therefore no residential handler exposure 

assessments are required. Assessments were performed using a short-term 

dermal and incidental oral endpoint of 15 mg/kg/day based on the NOAEL from a 

prenatal developmental toxicity study in rats and an intermediate-term endpoint 

of 7.6 mg/kg/day based on the NOAEL from a 90-day dietary toxicity study in 

rats. Dermal absorption was assumed to be 1.27% based on the in vivo/in vitro

relationship between the rat and human dermal absorption systems. The 

maximum residential exposure to adults was due to gardening activities using 
10

greenhouse and nursery treated plants, resulting in short- and intermediate-term 

residential MOEs of 27,780 and 14,075, respectively. The maximum residential 

exposure to youths age 6-11 years was due to gardening activities using 

greenhouse and nursery treated plants, resulting in short- and intermediate-term 

residential MOEs of 40,583 and 20,562, respectively. The maximum residential 

exposure to youths age 11-16 years was due activities on treated golf courses, 

resulting in short- and intermediate-term residential MOEs of 496,163 and 

251,389, respectively. The maximum residential exposure to children 1-2 years 

was due to play activities on treated turf, resulting in short- and intermediate-term 

residential MOEs of 12,030 and 6,095, respectively.

D. Cumulative Effects

Cumulative Exposure to Substances with a Common Mechanism of 

Toxicity. Section 408(b)(2)(D)(v) requires that, when considering whether to 

establish, modify, or revoke a tolerance, the Agency consider “available 

information” concerning the cumulative effects of a particular pesticide’s residues 

and “other substances that have a common mechanism of toxicity”. The EPA 

does not have, at this time, available data to determine whether benzovindiflupyr 

has a common mechanism of toxicity with other substances or how to include 

this pesticide in a cumulative risk assessment. For the purposes of this tolerance 

action, the EPA has not assumed that benzovindiflupyr has a common 

mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population. The acute aggregate exposure calculation for 

proposed uses of benzovindiflupyr provided an MOE of 10,390 or 1.0% of the 

aRfD (Benchmark MOE = 100; aRfD = 0.15 mg/kg-bw/day) for the U.S. 

population. The chronic aggregate exposure calculation for proposed uses of 

benzovindiflupyr provided an MOE of 73,134 or 0.1% of the cRfD (Benchmark 

MOE = 100; cRfD = 0.05 mg/kg-bw/day) for the U.S. population. Since the 

aggregate MOEs exceed the benchmark MOE of 100, Syngenta believes that 

there is a reasonable certainty that no harm will occur to the U.S. Population from 

acute, short-term, intermediate-term, or chronic aggregate exposures arising 

from the proposed uses for benzovindiflupyr.

2. Infants and children. The acute aggregate exposure calculation for 

proposed uses of benzovindiflupyr provided an MOE of 4,869 or 2.1% of the 

aRfD (Benchmark MOE = 100; aRfD = 0.15 mg/kg-bw/day) for children 1-2 years 

old (the most sensitive subpopulation for the acute assessment). The short-term 

aggregate assessment resulted in an MOE of 10,886 for the children (1-2 years 

old) population subgroup (Benchmark MOE = 100). The intermediate-term 

aggregate assessment resulted in an MOE of 5,516 for the children (1-2 years 

old) population subgroup (Benchmark MOE = 100). The chronic aggregate 
11

exposure calculation for proposed uses of benzovindiflupyr provided an MOE of 

37,292 or 0.3% of the cRfD (Benchmark MOE = 100; cRfD = 0.05 mg/kg-bw/day) 

for the children (1-2 years old) (the most sensitive subpopulation for the chronic 

assessment). Since the worst-case aggregate MOE of 5,516 exceeds the 

benchmark MOE of 100, Syngenta believes that there is a reasonable certainty 

that no harm will occur to infants and children from acute, short-term, 

intermediate-term, or chronic aggregate exposures arising from the proposed 

uses for benzovindiflupyr

F. International Tolerances

There are currently no Maximum Residue Limits (MRLs) set for 

Benzovindiflupyr for crops by the Codex Alimentarius Commission and 

international MRLs for the fungicide Benzovindiflupyr have not been established.