EPA Registration Division contact: Andrew Ertman, 703-308-9367 

Interregional Research Project Number 4 (IR-4)

PP No. 1E7904

 EPA has received a pesticide petition (PP No. 1E7904) from Interregional 

Research Project No. 4 (IR-4), 500 College Road East, Suite 201 W, Princeton, NJ 08540

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 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 

raw agricultural commodity crop group, vegetable, cucurbit, group 9 at 0.03 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. In the appropriate growing areas of the US, IR-4 

conducted magnitude of residue studies in cucumber (pickling and slicing 

varieties), cantaloupe, and squash, the representative commodities for crops in the 

crop group, vegetable, cucurbit, group 9. A total of approximately 0.090 lb ai/A 

was applied in six foliar applications of Proclaim 5SG at a rate of approximately 

0.015 lbs ai/A. Raw agricultural commodities (RAC) samples were harvested 6-8 

days after the last treatment. In addition, IR-4 also conducted residue decline 

trials in 4 locations (3 cucumber and 1 squash). In these decline trials, crop 

samples were collected at 0, 3, 10, 13, and/or 14 days PHI. 

There were no detectable residues of any of the six emamectin benzoate analytes 

in the cucumber and squash RAC samples harvested at 6-8 days PHI. For the 

cantaloupe RAC samples harvested at 6-8 days PHI, one of the six analytes, 
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NOA-426007 (emamectin B1a), was present in amounts above the lowest limit of 

method validation (LLMV). All other analytes were below the LLMV. In the 

decline trials, squash taken at 0 days PHI showed combined emamectin B1a + 

8,9Z residues above the LLMV (all other analytes were below the LLMV) and 

declined to below the LLMV for all analytes at the subsequent sampling events. 

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

metabolism, metabolite toxicology, and endocrine disruption of emamectin benzoate can 

be found in the final rule published in the Federal Register of July 9, 2003 (68 FR 

40791) 

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), and cottonseed oil (0.39X) were used in these 

assessments. All other processing factors used DEEMTM Version 7.87 default 

values. All consumption data for these assessments was 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 uses for 

emamectin benzoate, a pending use on outdoor nursery ornamentals, and a 

proposed new use on cucurbit vegetables (Crop Group 9). The intended use 

pattern includes up to six applications at a rate of up to 0.015 lbs. a.i./A 

(maximum seasonal rate = 0.09 lbs. a.i./A) with a pre-harvest interval (PHI) of 7 

days. Percent crop treated (%CT) values were estimated based upon economic, 

pest, and competitive pressures. 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 multi-level feeding studies (beef, dairy, and swine) or from 

metabolism studies (poultry).

i. Food. 

Acute Exposure. The emamectin benzoate acute food risk assessment 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 
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only) exposure to the U.S. population resulted in a MOE of 557 (53.8% 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 to residues arising from all current, 

pending, and proposed uses for emamectin benzoate. 

Chronic Exposure. The emamectin benzoate chronic food risk assessment was 

performed for all population subgroups using 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), based on moribund sacrifices, clinical signs of neurotoxicity, 

decreases in body weight and food consumption and histopathological lesions in 

the sciatic nerve, 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/kgbw/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 13,801 (7.2% 

of the cRfD of 0.000075 mg/kg-bw/day). The most sensitive population subgroup was children 1-2 years old, with a MOE of 6,010 (16.6% 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 

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 uses plus the proposed use on cucurbits 

were determined. Based on the SCI-GROW modeling, the groundwater EDWC 

for emamectin is 5.40E-04 ppb (acute and chronic) based on the current and 

pending/proposed uses on Brassica head and stem vegetables, Brassica leafy 

vegetables, fruiting vegetables, leafy vegetables, outdoor nursery grown 
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herbaceous and woody ornamentals, and cucurbits. 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 exceed 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 5,769 (5.2% 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 

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 that result in residential 

exposures. All proposed and pending uses, including professionally applied tree 

injection and professionally applied cockroach gel bait, are not expected to result 

in residential exposures for any population subgroup. 
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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 exposure from all established and proposed emamectin benzoate uses would 

result in a MOE of 519 (57.8% of the aRfD) for the U.S. population, which 

exceeds the Benchmark MOE of 300. The chronic dietary exposure analysis 

(food plus water) showed that exposure from all established and proposed 

emamectin benzoate tolerances resulted in a MOE of 6,250 (16.0% of the cRfD) 

which 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 residues arising from all current, pending, 

and proposed uses for emamectin benzoate. 

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

showed that exposure from all established and proposed emamectin benzoate uses 

would result in a MOE of 311 (96.4% of the aRfD) for the most sensitive 

population subgroup, children 1-2 years old, which exceeds the Benchmark MOE 

of 300. The chronic aggregate dietary (food and water) exposure analysis showed 

that exposure from all established and proposed emamectin benzoate uses would 

result in a MOE of 2,344 (42.7% of the cRfD) for the most sensitive population 

subgroup, all infants <1 year old, which 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 or on any commodities, so harmonization of international tolerances is not an issue. 
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