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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Thomas C. Harris, harris.thomas@epa.gov, (703) 308-9423

Syngenta Crop Protection, LLC

PP 2E8018 

EPA has received a pesticide petition (PP 2E8018) from Syngenta

Crop Protection. LLC, P.O. Box 18300, Greensboro, NC 27419 requesting, 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

by establishing a tolerance for residues of

emamectin benzoate, 4'-epi-methylamino- 4'-deoxyavermectin B1 benzoate (a mixture 

of a minimum of 90% 4'-epi-methylamino-4'- deoxyavermectin B1a and a maximum of 

10% 4'-epi-methlyamino-4'deoxyavermectin B1b benzoate), and its metabolites 8,9 

isomer of the B1a and B1b component of the parent insecticide in or on the processed 

agricultural commodity imported wine at 0.005 parts per million (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. The metabolism of emamectin benzoate in plants has been 

studied and the nature of the residue has been determined in lettuce, cabbage, and 

sweet corn. The major portion of the residue is parent compound and its delta 8,9- 

photoisomer. The metabolism of emamectin has also been investigated in goats 

and poultry to characterize the fate of residues that may be present in animal feed 

items 

2. Analytical method. Adequate analytical methods (HPLC-fluorescence methods) 

are available for enforcement purposes.

3. Magnitude of residues. Sixteen residue trials, in which emamectin benzoate 

was applied to wine grapes, were conducted in Europe and were designed to 

comply with the EU residue chemistry data requirements. Specifically, the trials 

were designed to quantify emamectin benzoate and metabolite residues in grapes 

based upon the worst case (maximum residue) use pattern in Europe. This worst 
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case use pattern included a maximum of 4 applications per season at a rate of 

14.25 g AI/ha/application. The maximum seasonal rate is 57 g AI/ha/season. The 

minimum retreatment interval is 14 days, and the minimum pre-harvest interval is 

7 days. Grapes were analyzed using the LC-LC-MS/MS method RAM 465/01 

with an LOQ of 0.001 ppm. For the normalized total residues of concern in or on 

grapes, the average value was 0.009 mg/kg and the maximum value was 0.031 

mg/kg. 

Trials in Australia and New Zealand were conducted to facilitate selection of a 

local use pattern for which the residues in grapes are less than the limit of 

quantification. The registered directions for use are: 

1. In Australia, a maximum of 2 applications with a maximum rate of 6.6 g 

AI/ha/season and a minimum pre-harvest interval of 56 days. 

2. In New Zealand, a maximum of 2 applications at a maximum rate of 4.0 g 

AI/ha/season with applications no later than the pre-bunch closure growth 

stage. 

The trial most relevant to the registered directions for use in Australia was 

conducted with two applications at 6.6 g AI/ha/application for a total of 13.2 g 

AI/ha/ season. This trial was conducted at 2x the registered application rate, and 

the measured residues are reported to be non-detectable (LOD = 0.005 mg/kg). 

The trial most relevant to the registered label in New Zealand was conducted with 

two applications; the first application at 80% cap fall and a second application at

pre-bunch closure, both at 80 g ai/ha. Total emamectin residue (B1a/8,9-Z + B1b) 

was measured as 0.0012 mg/kg. The application rate for this use of 80 g ai/ha is

40-fold greater than the registered directions for use. It is strongly believed, if the 

applications had been made according to the currently labeled directions for use, 

the total measured residues in grapes would have been well below the limit of 

detection (<0.005 mg/kg). 

Two trials were conducted in Italy to determine emamectin residues in grapes and 

wine at different pre-harvest intervals. In both of the Italian studies, residues were 

<0.001 ppm in the grapes harvested at 7 and 21 days after application and in the 

corresponding wine samples. In one of the two studies, residues were 0.004 ppm 

in grapes harvested 0-days after the application and <0.001 ppm in the 

corresponding wine sample. In the second of the two studies, residues in the 0-

day PHI grape sample and corresponding wine sample were 0.024 and 0.002 ppm, 

respectively. These data demonstrate that emamectin benzoate does not concentrate 

in wine. 

Two trials were conducted in South Australia and Victoria in red and white grape 

varieties to determine the sum of residues of emamectin B1a plus emamectin B1b

in grapes, grape juice and wine. Two applications of emamectinbenzoate were 

applied at 150 or 300 g ai/ha at 7 day intervals to bunch closure (BBCH 77). The 
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product was applied at dilute (~1000 l/ha) and concentrate (~250 l/ha) water 

volumes. The residue data include only one quantifiable residue. Grapes from 

one of the two sites receiving two low volume treatments at a rate of 13.2 g 

AI/ha/application for a total of 26.4 g AI/ha/season with a 98-day PHI were 

determined to have a residue of 0.0009 mg/kg emamectin B1a (at the limit of 

quantification) in a single replicate. The measured emamectin B1a residues in 

juice and wine from the same trials were determined to be less than the limit of 

quantification. Residues of emamectin B1b in all trials were, without exception, 

determined to be less than the limit of quantification. These data suggest that 

residues of emamectin B1a do not concentrate in grape juice or wine and

calculation of a residue processing factor for grape juice or wine is not needed.

B. Toxicological Profile A full description of the studies regarding the toxicity, animal 

metabolism, and metabolite toxicology, of emamectin benzoate can be found in EPA’s 

memorandum, “Emamectin Benzoate. Human Health Risk Assessment Scoping 

Document in Support of Registration Reviews,” PC Code: 122806, Decision No.: 

444324, DP Barcode: D385990, dated June 16, 2011. 

C. Aggregate Exposure

1. Dietary exposure. Tier III acute and chronic dietary exposure evaluations were 

made for emamectin benzoate using the Dietary Exposure Evaluation Model 

software with the Food Commodity Intake Database (DEEM-FCIDTM, version 

2.16) from Exponent. Empirically derived processing factors for apple juice 

(0.05X), apple pomace (4.3X), cottonseed oil (0.39X), and wine (0.088X) were 

used in these assessments. All other processing factors used DEEMTM Version 

7.87 default values. All consumption data for these assessments were taken from 

the USDA’s Continuing Survey of Food Intake by individuals (CSFII) with the 

1994-96 consumption database and the Supplemental CSFII children’s survey 

(1998) consumption database. These exposure assessments included all current 

and pending uses for emamectin benzoate plus this proposed new tolerance for 

residues of emamectin benzoate in imported wine. Use of emamectin benzoate on 

grapes grown for wine is approved in Europe, Australia, and New Zealand. 

Directions for use that are on the approved labels for emamectin-based end-use 

products specify up to 4 applications at a rate of up to 15 g a.i./ha per application 

for a maximum of 60 g ai/ha per season. A minimum of 7 days between the last 

application and harvest is the (PHI) These assessments assumed a tolerance of 

0.0035 ppm for residues of emamectin benzoate in imported wine. This value was 

based on an (estimated 0.04 ppm tolerance in wine grapes (OECD) multiplied by 

a 0.088X grape-to-wine processing factor). A percent crop treated value of 100% 

%CT was assumed for wine and sherry. Note, it is not necessary to consider 

secondary residues in meat, milk and eggs since wine is not a livestock feed item. 

However, secondary residues in meat, milk, and eggs were estimated by 

constructing “maximum reasonably balanced diets” using the OPPTS 860.1000 

Table 1 feedstuffs (June 2008 revision) and transfer information taken from multilevel feeding studies (beef, dairy, and swine) or from metabolism studies (poultry 
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i. Food.

Acute Exposure. The acute dietary risk assessment for emamectin benzoate was 

performed for all population subgroups using an acute reference dose of 0.00025 

mg/kg-bw/day from a 15 day neurotoxicity study in mice (LOAEL of 0.1 mg/kgbw/day), based on tremors observed beginning on day 3 of dosing, using an 

endpoint of 0.075 mg/kg-bw/day and an uncertainty factor of 300X (100X for 

intra- and inter-species variability and 3X for absence of a NOAEL). No 

additional FQPA safety factor was applied. For the purpose of the aggregate risk 

assessment, exposure values were expressed in terms of margin of exposure 

(MOE), calculated by dividing the 0.075 mg/kg-bw/day endpoint by the exposure 

for each population subgroup. In addition, exposures were expressed as a percent 

of the acute reference dose (%aRfD). At the 99.9th percentile, acute dietary (food 

only) exposure to the U.S. population resulted in a MOE of 555 (54.0% of the 

aRfD of 0.00025 mg/kg-bw/day). The most sensitive population sub-group was 

children 1-2 years old, with a MOE of 326 (91.9% of the aRfD of 0.00025 mg/kgbw/day). Since the Benchmark MOE for this assessment is 300 and since EPA 

generally has no concern for exposures above the benchmark or below 100% of 

the reference dose, Syngenta believes that there is a reasonable certainty that no 

harm will result from acute food exposures food exposure to residues arising from 

all current, pending, and proposed uses for emamectin benzoate. 

Chronic Exposure. The chronic dietary risk assessment for emamectin benzoate 

was performed for all population subgroups based on a chronic reference dose of 

0.000075 mg/kg-bw/day from a 15 -day neurotoxicity study in mice (LOAEL of 

0.1 mg/kg-bw/day), (LOAEL was based on moribund sacrifices, clinical signs of 

neurotoxicity, decreases in body weight and food consumption and 

histopathological lesions in the sciatic nerve,) The risk assessment was performed 

by using an endpoint of 0.075 mg/kg-bw/day and an uncertainty factor of 1000X 

(100X for intra- and inter-species variability and an additional 10X for absence of 

a NOAEL). No additional FQPA safety factor was applied. For the purpose of 

the aggregate risk assessment, exposure values were expressed in terms of margin 

of exposure (MOE), calculated by dividing the 0.075 mg/kg-bw/day endpoint by 

the exposure for each population subgroup. In addition, exposures were 

expressed as a percent of the chronic reference dose (%cRfD). Chronic food 

exposure to the U.S. population resulted in a MOE of 12,744 (7.8% of the cRfD 

of 0.000075 mg/kg-bw/day). The most sensitive population sub-group was 

children 1-2 years old, with a MOE of 6,005 (16.7% of the cRfD of 0.000075 

mg/kg-bw/day). Since the Benchmark MOE for this assessment is 1,000 and 

since EPA generally has no concern for exposures above the benchmark or below 

100% of the reference dose, Syngenta believes that there is a reasonable certainty 

that no harm will result from chronic food exposures to residues arising from all 

current, pending, and proposed uses for emamectin benzoate. 

Cancer Risk. No cancer risk assessment was performed for emamectin benzoate, 

which has been classified as a “not likely” human carcinogen based on the lack of 

evidence of carcinogenicity in male and female rats or male and female mice at 
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doses that were judged to be adequate to assess the carcinogenic potential of the 

chemical. 

ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of 

emamectin benzoate (expressed as combined total residues of parent plus 8,9- Z 

isomer, AB, MAB, and FAB) were determined using Tier l SCI-GROW which 

estimates pesticide concentration in ground water and Tier II PRZM/EXAMS 

which estimates pesticide concentration in surface water. EDWCs for emamectin 

from the currently registered and pending use on cucurbits and on outdoor nursery 

grown herbaceous and woody ornamentals were determined. Based on the SCIGROW modeling, the groundwater EDWC for emamectin is 5.40E-04 ppb (acute 

and chronic). Based on Tier II PRZM/EXAMS modeling for surface water, the 

pending use on outdoor nursery grown herbaceous and woody ornamentals 

provided an acute EDWC of 1.096 ppb (no Percent Cropped Area (PCA) 

adjustment) and the currently registered tomato use provided a chronic EDWC of 

0.347 ppb (corrected for 0.87 PCA). Since the surface water EDWCs exceeded

the ground water EDWC, the surface water values were used for risk assessment 

purposes and will be considered protective for any ground water exposure 

concerns. 

Acute Exposure from Drinking Water: Syngenta utilized the Monte-Carlo 

probabilistic technique for this exposure assessment, using the nursery standard 

PRZM scenario. The complete distribution of estimated drinking water 

concentrations for the period from January 1, 1961 to January 1, 1991 (n = 

10,958) were extracted from the EDWC prediction database and were utilized in 

the DEEM-FCIDTM software as residue distribution files (RDF) for “water, direct 

and indirect, all sources.” Predicted EDWC results were not adjusted for PCA. 

Drinking water exposures at the 99.9th percentile were determined by taking the 

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

exposures (food only) for each population subgroup. Acute drinking water 

exposure to the U.S. population resulted in a MOE of 7,500 (4.0% of the aRfD of 

0.00025 mg/kg-bw/day). The most sensitive sub-population was children 3-5 

years old, with a MOE of 5,357 (5.6% of the aRfD of 0.00025 mg/kg-bw/day). 

Since the Benchmark MOE for this assessment is 300 and since EPA generally 

has no concern for exposures above the benchmark or below 100% of the 

reference dose, Syngenta believes that there is a reasonable certainty that no harm 

will result from acute drinking water exposures to residues arising from all 

current, pending, and proposed uses for emamectin benzoate.. 

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

0.347 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 MOE of 10,254 

(9.8% of the cRfD of 0.000075 mg/kg-bw/day). Chronic drinking water exposure 

to the most exposed sub-population (infants <1 year old) resulted in a MOE of 

3,128 (32.0% of the cRfD of 0.000075 mg/kg-bw/day). Since the Benchmark 
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MOE for this assessment is 1,000 and since EPA generally has no concern for 

exposures above the benchmark or below 100% of the reference dose, Syngenta 

believes that there is a reasonable certainty that no harm will result from chronic 

drinking water exposures to residues arising from all current, pending, and 

proposed uses for emamectin benzoate. 

2. Non-dietary exposure. There are no current uses or uses pending EPA approval 

that result or will result in residential exposures. 

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”. Syngenta did not 

perform a cumulative risk assessment as part of this tolerance action for 

emamectin because HED has not yet determined that there are any other chemical 

substances that have a mechanism of toxicity common with that of emamectin. 

For purposes of this tolerance action, EPA has assumed that emamectin does not 

have a common mechanism of toxicity with other substances. 

E. Safety Determination

1. U.S. population. The acute dietary exposure analysis (food plus water) showed 

that dietary exposure associated with all of the approved and pending uses of 

emamectin benzoate as well the proposed tolerance for emamectin benzoate in 

imported wine would result in an acceptable MOE of 518 (57.9% of the aRfD) for 

the U.S. population, because it is higher than the Benchmark MOE of 300. The 

chronic dietary exposure analysis (food plus drinking water) showed that chronic 

exposure associated with all of the approved and pending uses of emamectin 

benzoate chronic exposure associated with the proposed tolerance for emamectin 

benzoate in wine resulted in an acceptable MOE of 5,769 (17.3% of the cRfD) 

because it exceeds the Benchmark MOE of 1,000. Based on the completeness 

and reliability of the toxicity data supporting these petitions, Syngenta believes 

that there is a reasonable certainty that no harm will result to the general U. S. 

population from aggregate exposure to potential residues arising from all of the 

approved and pending uses for emamectin benzoate plus residues of emamectin 

benzoate that may be present in imported wine. 

2. Infants and children. The acute dietary exposure analysis (food plus drinking 

water) showed that exposure to emamectin benzoate associated with the approved 

and pending uses and exposure associated with this proposed import tolerance 

would result in an MOE of 309 (96.9% of the aRfD) for the most sensitive 

population subgroup, children 1-2 years old, which is acceptable because it 

exceeds the Benchmark MOE of 300. The chronic aggregate dietary (food and 
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drinking water) exposure analysis showed that exposure associated with the 

approved and pending uses of emamectin benzoate as well as the exposure 

associated with the proposed tolerance for emamectin benzoate in wine an MOE 

of 2,344 (42.7% of the cRfD) for the most sensitive population subgroup, all 

infants <1 year old, which is acceptable since it exceeds the Benchmark MOE of 

1,000. Based on the completeness and reliability of the toxicity data supporting 

these petitions, Syngenta believes that there is a reasonable certainty that no harm 

will result to infants and children from aggregate exposure to residues arising 

from all current, pending, and proposed uses for emamectin benzoate.

F. International Tolerances

There are no Codex maximum residue limits (MRLs) established for emamectin benzoate 

in wine, so harmonization of international tolerances is not an issue.