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# 2E8123

EPA has received a pesticide petition PP# 2E8123 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 an import tolerance for residues of Benzovindiflupyr

(SYN545192) in or on the raw agricultural commodity coffee, bean, green at 0.09

parts per million (ppm) and sugarcane, cane at 0.04 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 benzovindiflupyr in all crops. Two radiocarbon labels 

were studied in each crop, with [

14C] labels positioned in the 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 dietary risk assessment. The corresponding definitions in commodities of 

animal origin are parent SYN545192 for monitoring and sum of SYN545192 and 

SYN546039 for dietary risk assessment. Method GRM042.03A (implemented as POPIT 

MET.125, POPIT MET.133 have used for analysis of SYN545192 and its metabolites 

SYN546039 in sugarcane and coffee samples, respectively. The limit of quantitation 

(LOQ) for method POPIT MET. 125 and POPIT MET. 133 were 0.005 and 0.01, 

respectively.

Both methods GRM042.03A and GRM042.04A for plant products have been developed 
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to 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 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. QuEChERS multi-residue method (EN 15662:2009) has been 

validated and independently validated for post-registration monitoring of SYN545192 for 

compliance with MRLs and import tolerances in plant and animal commodities at an 

LOQ of 0.01 mg/kg.]

3. Magnitude of residues. [twenty four supervised residue trials were conducted 

on coffee and sugarcane (12 trial/each crop) in 2010/11 in six provinces of Brazil using 

SYN545192 formulated as A17961A (an EC formulation containing SYN545192 and 

azoxystrobin) or A18126B (a WG formulation containing SYN545192 and 

azoxystrobin). Detected residues of benzovindiflupy in all crops support the proposed 

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 than 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 US EPA category

II for oral and US EPA 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 treatment-related chromosomal aberrations. In vivo, SYN545192 was 

found to be non-clastogenic in the rat bone marrow micronucleus assay and did not 

induce micronuclei in bone marrow cells.]
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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 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. 

In the definitive prenatal developmental toxicity study in rabbits, 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 inlife effects (reduced body weights, food consumption and food utilization) at 750 ppm 

and above. Covariant liver weights adjusted for body weight 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 
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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, changes in clinical chemistry parameters and mucosal hyperplasia in the rectum 

and colon at 300 and 500 ppm. 

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. Male and female Beagle dogs were dosed orally 

by capsule with SYN545192 at 0, 30, 375 or 750 mg/kg/day for a period of 13 weeks. At 

375 and 750 mg/kg/day, there was an initial body weight loss, decreased food 

consumption, decreased body weight gain and some effects on clinical biochemistry. 

Mild clinical signs were observed in dogs at 375 and 750 mg/kg/day. There were no 

effects at 30 mg/kg/day which is considered to be the no effect level (NOEL) for this 

study.]

5. Chronic toxicity. [Benzovindiflupyr (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 of 0, 25, 100 and 600 ppm (males) or 400 ppm 

(females).

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

observed in both sexes at the top dose. . Clinical chemistry values of ALP, ALT and 

AST 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).

Supplemental mechanistic studies were conducted in rats. These studies demonstrated a 
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Mode of Action (MOA) for induction of thyroid tumors at high dose levels in male rats 

that is secondary to enhanced clearance of thyroid hormones via induction of liver 

metabolizing enzymes. This MOA is not considered relevant to humans. 

In a carcinogenicity study with SYN545192, 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. Statistically significantly lower group mean body weight was observed in males 

treated with 200 ppm during the first 7 weeks of the study.

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 benzovindiflupyr (SYN545192) 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 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 three principal routes,

i) N-pyrazole demethylation of SYN545192 and

ii) Oxidation resulting in monohydroxylation of the alicyclic ring

iii) 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 and in vitro genotoxicity

(Bacterial reverse mutation). SYN546039 was not acutely toxic to rats by oral route 

(MLD>2000 mg/kg) and was not genotoxic in vitro. These data indicate that 
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SYN546039 is of lower toxicity than parent SYN545192 and is not considered to be of

toxicological relevance.

Metabolites CSAA798670 and CSCD465008 (pyrazole acid metabolites 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 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 OPPTS Guideline 

870.7800, to provide information on suppression of the immune system which might 

occur as a result of repeated exposure to a test chemical. Treatment of female CD-1 mice 

with benzovindiflupyr on a continuous basis in the diet at dose levels of 0, 100, 200 and 

400 ppm 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 (AFC) 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 Sub-Group 1C), cucurbit vegetables 

(Crop Group 9), fruiting vegetables (Crop Group 8-10), 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 
7

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 in a 

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-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.
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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 (SCI-GROW v2.3), was used. The maximum field 

application rate for multiple crops including corn, cucurbits, fruiting 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). SCI-GROW calculated a 

groundwater EDWC (acute and chronic) of 0.00428 μg/L (ppb). Since the surface water 

EDWCs exceed the ground water EDWC, the 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 subpopulation 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 
9

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 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 to activities on treated golf courses, resulting in short- and intermediateterm 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 shortand 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 
10

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 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/kgbw/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.