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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS 

PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Jessica Rogala (703) 347-0263

Syngenta Crop Protection, LLC

PP 2F8009

EPA has received a pesticide petition (PP 2F8009) from Syngenta Crop Protection LLC 

P.O. Box 18300; Greensboro, NC 27419 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 amending the tolerances for the combined residues of the insecticide avermectin 

B1(a mixture of avermectins containing greater than or equal to 80% avermectin B1a (5-

O- demethyl avermectin A1) and less than or equal to 20% avermectin B1b (5-Odemethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)) and its delta-8,9-

isomer in or on cotton, delinted seed and cotton, gin by-products from 0.005 parts per 

million (ppm) to 0.015 parts per million (ppm) and strawberry from 0.02 parts per 

million (ppm) to 0.06 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 abamectin in plants is adequately 

understood and the residues of concern include the parent insecticide abamectin (also 

referred to as avermectin B1 which is a mixture of a minimum of 80% avermectin B1a and 
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a maximum of 20% avermectin B1b) and the delta 8,9-isomer of the B1a and of the B1b

components of the parent insecticide.

2. Analytical method. The analytical methods involve homogenization, filtration, 

partition, and cleanup with analysis by high performance liquid chromotography (HPLC)-

fluorescence detection. The methods are sufficiently sensitive to detect residues at or 

above the tolerances proposed. All methods have undergone independent laboratory 

validation.

3. Magnitude of residues. Cotton: 

In 2009 nine magnitude of residue (MOR) studies in cotton were conducted with the SC 

formulation of abamectin. One trial was located in Virginia, 2 trials in Arkansas, 4 in 

Texas, and 2 in California. 

In 2010, 3 additional trials in cotton with this formulation were conducted to 

complete the number of geographical locations that the EPA requires for magnitude of 

residue studies, One trial was located in Louisiana, 1 in Texas, and 1 in California. 

The SC formulation of abamectin was applied foliarly to cotton 2 times at a rate of 0.019 

lb ai/A with a 21-day interval between applications. Cotton was sampled 20 days after 

the last application. In addition to the proposed target interval, undelinted cottonseed 

and cotton gin trash were harvested in the decline trials. In the processing study, 

undelinted seed was processed into cotton hulls, cotton meal, and refined cottonseed 

oil. 

Samples were analyzed for abamectin (a mixture containing 80% parent B1a 

(NOA422601) and 20% B1b (NOA421704) and its delta-8,9 isomer (8,9-Z-isomer of 

parent B1a. The maximum residues of abamectin in undelinted cotton seed were 0.01 

ppm for avermectin B1a and <0.002 ppm for B1b. For cotton gin by-products, the 

maximum residues of abamectin were 0.68 ppm for B1a and 0.005 for B1b. In the 

cotton processing study, there was no concentration of abamectin residues in the 

processed fractions (hulls, meal, refined oil). 
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In the cotton MOR study (9 trials) conducted in 2009 with the SC formulation, there were 

some abamectin residues in undelinted seed (TX) and in cotton, gin by-producs (CA) that 

exceeded the established abamectin tolerance for undelinted seed (0.005 ppm) and the 

established tolerance for abamectin in cotton gin by-products (0.15 pm). 

In the cotton MOR trials with the SC formulation which were conducted in 2010 (3 

trials), there were no abamectin residues in cotton, undelinted seed that exceeded the 

established abamectin tolerance and no abamectin residues in cotton, gin by-products that 

exceeded the established abamectin tolerance (0.15 ppm), however in one trial (TX) the 

level of abamectin residue in gin by-products was at the tolerance level of 0.15 ppm. .

In the cotton processing study, there was no concentration of abamectin residues in 

cotton, processed fractions (hulls, meal, refined oil). 

Results of these MOR studies in cotton with the SC formulation of abamectin, indicate 

the established tolerances for abamectin in cotton, undelinted seed and in cotton, gin byproducts, need to be increased. There is no need for a tolerance in cotton processed 

fractions. 

.

Two magnitude of residue (MOR) trials with the SC formulation of abamectin in 

strawberries were conducted. One trial was located in North Carolina and the other trial 

was located in California The SC formulation of abamectin was applied to strawberries 4 

times at a rate of 0.19 lb. ai/A per application. There was a 7-day interval between the 

first and second applications, a 21-day interval between the second and third 

applications, and a 7-day interval between the third and fourth applications. 

Strawberries were sampled 3 days after the last application. 

Samples from all of the studies (12 total) were analyzed for abamectin (a mixture 

containing 80% parent B1a (NOA422601) and 20% B1b (NOA421704) and its delta-8,9 

isomer (8,9-Z-isomer of parent B1a. The maximum residues of abamectin in 

strawberries were 0.04 ppm for avermectin B1a and 0.04 ppm for B1b
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Results of these MOR studies for strawberries with the SC formulation of abamectin as 

the test material, indicate the established tolerance for abamectin in strawberry (0.02 

ppm) needs to be increased. 

B. Toxicological Profile

1. Acute toxicity. The database includes the following studies with Syngenta’s 

technical abamectin products:

Abamectin Technical: 

i. A rat acute oral study with an LD50 of 13.6 mg/kg.

ii. A rat acute oral study with an LD50 of 214-232 mg/kg.

iii. A rabbit acute dermal study with an LD50 of 2000 mg/kg.

iv. A rat acute inhalation study with an LC50 of 0.21 mg/L (nose only).

v. A primary eye irritation study in rabbits which showed no irritation.

vi. A primary skin irritation study in rabbits which showed slight irritation.

vii. A dermal sensitization study (Buehler) in guinea pigs which was negative.

Abamectin Technical II

i. A rat acute oral study with an LD50 of 372.5 mg/kg

ii. A rat acute dermal study with an LD50 of >200 mg/kg but <2000 mg/kg 

ii.A rat acute inhalation study with an LC50 of >0.0518 mg/L (nose only)
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v. A primary eye irritation study in rabbits which showed no irritation.

vi. A primary skin irritation study in rabbits which showed slight irritation.

vii. A dermal sensitization study (Buehler) in guinea pigs with Abamectin Technical 

supports the registration of this technical.

2. Genotoxicty. The Ames assays conducted with and without metabolic 

activation were both negative. The V–79 mammalian cell mutagenesis assays conducted 

with and without metabolic activation did not produce mutations. In an alkaline 

elution/rat hepatocyte assay, abamectin was found to induce single strand DNA breaks 

without significant toxicity in rat hepatocytes treated in vitro at doses greater than 0.2 

millimole per liter (mM). This in vitro dose of 0.2 mM is biologically unobtainable in vivo, 

due to the toxicity of the compound. However, at these potentially lethal doses, in vivo

treatment did not induce DNA single strand breaks in hepatocytes. In the mouse bone 

marrow assay, abamectin was not found to induce chromosomal damage. There are 

also, many studies and a great deal of clinical and followup experience with regard to 

ivermectin, a closely similar human and animal drug.

3. Reproductive and developmental toxicity. In a 2-generation study in rats the 

NOAEL was established at 0.12 mg/kg/day in pups based upon retinal folds, decreased 

body weight (bwt), and mortality. The NOAELs for systemic and reproductive toxicity 

were 0.4 mg/kg/day. In the 1-generation reproduction study in rats with the delta 8,9-

isomer, the NOAEL was 0.4 mg/kg/day and the lowest observed adverse effect level

(LOAEL) was greater than 0.4 mg/kg/day highest dose tested (HDT). In an oral 

developmental toxicity study in rabbits the maternal NOAEL was 1.0 mg/kg/day based 

upon decreased body weights and tremors. The fetal NOAEL was 1.0 mg/kg/day based 

upon clubbed feet. In an oral developmental toxicity study in rats the maternal and fetal 

NOAEL was 1.6 mg/kg/day, the HDT. In an oral developmental toxicity study the 

maternal NOAEL in CF-1 mice that expressed P-glycoprotein was greater than 1.5 

mg/kg/day, the highest and only dose tested. No cleft palates were observed in fetuses 

that expressed normal levels of P-glycoprotein, but fetuses with low or no levels of Pglycoprotein had increased incidence of cleft palates. In a developmental neurotoxicity 

study in rats the maternal NOAEL was 0.4 mg/kg/day, the HDT, and the offspring NOAEL 

was 0.12 mg/kg/day with an offspring LOAEL of 0.2 mg/kg/day based on slight pup body 
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weight loss. In a second developmental neurotoxicity study in rats the maternal NOAEL 

was 0.4 mg/kg/day, the HDT, and the offspring NOAEL was 0.2 mg/kg/day with an 

offspring LOAEL of 0.4 mg/kg/day based on decreased body weight in both sexes. There 

was no evidence of neurotoxicity in the offspring.

4. Subchronic toxicity. Subchronic toxicity studies included the following:

i. A rat 14–week oral toxicity study with a NOAEL of 0.4 mg/kg/day, the HDT.

ii. A dog 12–week feeding study with a NOAEL of 0.5 mg/kg/day based upon mydriasis.

iii. A dog 18–week oral study with a NOAEL of 0.25 mg/kg/day based upon mortality.

5. Chronic toxicity. A rat 53–week carcinogenicity feeding study was negative for 

carcinogenicity, with a NOAEL of 1.5 mg/kg/day based upon tremors. A CD–1 mouse 94–

week carcinogenicity feeding study was negative for carcinogenicity, with a NOAEL of 4 

mg/kg/day based upon decreased body weights. A dog 53–week chronic feeding study 

resulted in a NOAEL of 0.25 mg/kg/day based upon mydriasis.

6. Animal metabolism. Rats were given oral doses of 0.14 or 1.4 mg/kg bwt/day 

of abamectin or 1.4 mg/kg bwt/day of the delta 8,9 isomer. Over 7–days, the 

percentages excreted in urine were 0.3–1% of the administered dose of abamectin and 

0.4% of the dose of the isomer. The animals eliminated 69–82% of the dose of 

abamectin and 94% of the dose of isomer in feces. In rats, goats, and cattle, unchanged 

parent compound accounted for up to 50% of the total radioactive residues in tissues. 

The 24-hydroxymethyl derivative of abamectin was found in rats, goats, and cattle 

treated with the compound and in rats treated with the delta 8,9 isomer, and the 3’’-Odemethyl derivative was found in rats and cattle administered abamectin and in rats 

administered the isomer.

7. Metabolite toxicology. There are no metabolites of concern based on a 

differential metabolism between plants and animals. The potential hazard of the 24-

hydroxymethyl or the 3’’-O-demethyl animal metabolites was evaluated in toxicology 

studies with abamectin photolytic break-down product, the delta 8,9-isomer.
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8. Endocrine disruption. [There is no evidence that abamectin is an endocrine 

disrupter. Evaluation of the rat multigenerational study demonstrated no effect on the 

time to mating or on the mating and fertility indices, suggesting no effects on the 

estrous cycle, on mating behavior, or on male or female fertility at doses up to 0.4 

mg/kg/day, the HDT. Furthermore, the range finding study demonstrated no adverse 

effect on female fertility at doses up to 1.5 mg/kg/day, the HDT. Similarly, chronic and 

subchronic toxicity studies in mice, rats, and dogs did not demonstrate any evidence of 

toxicity to the male or female reproductive tract, or to the thyroid or pituitary (based 

upon organ weights and gross and histopathologic examination). In the developmental 

studies, the pattern of toxicity observed does not seem suggestive of any endocrine 

effect. Finally, experience with ivermectin in breeding animals, including sperm 

evaluations in multiple species, shows no adverse effects suggestive of endocrine 

disruption. 

The EPA notified registrants of the EPA’s first group of specified active ingredients and 

manufacturers of the EPA’s first group of specified inert ingredients that the Agency 

was initiating the Endocrine Disruptor Screening Program for these compounds. In 2010 

the EPA issued Data-Call In’s the endocrine assays required for specified active 

ingredients including abamectin. The Abamectin EDSP Consortium is generating the 

required assays 

C. Aggregate Exposure

1. Dietary Exposure. Acute and chronic Tier III dietary exposure evaluations were 

made for abamectin using the Dietary Exposure Evaluation Model (DEEM-FCIDTM, 

version 2.03) from Exponent. 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 Tier III assessments included all currently registered 

Section 3 foliar crop uses including: apples, avocado, celeriac, chives, citrus fruit (Crop 

Group 10), cotton, cucurbits (Crop Group 9), dry beans (seed), dry bulb onions, fruiting 
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vegetables (Crop Group 8), grapes, herbs (crop subgroup 19A, except chives), hops, leafy 

vegetables except Brassica (Crop Group 4), mint (peppermint and spearmint), pears, 

pistachios, stone fruit (Crop Group 12), strawberries, tree nuts (Crop Group 14), and 

tuberous and corm vegetables (Crop Group 1C) .Abamectin is currently registered for 

seed treatment (ST) uses on corn, cotton, cucurbits, tomatoes, and soybean. Abamectin 

is also registered for use in food handling establishments), and for cattle ear-tag use. 

Established tolerances for abamectin in or on cotton and strawberry are based on 

residue studies with the EC formulation. This petition to amend these tolerances 

applies to the proposed use of the SC formulation of abamectin on these crops. For 

these exposure assessments, residue data were taken from cotton and strawberry field 

trials in which the SC formulation of abamectin was applied at the maximum intended 

use rate and samples were harvested at the minimum pre-harvest interval (PHI) to 

obtain maximum residue values. 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. 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. 

i. Food Acute Exposure. The abamectin acute dietary (food only) risk assessment was 

performed for all population subgroups with an acute reference dose of 0.005 mg/kgbw/day based on a 12-week dose-range finding study in dogs with a No Observed 

Adverse Effect Level (NOAEL) of 0.5 mg/kg-bw/day and an uncertainty factor of 100X. 

The 100-fold safety factor includes intra- and interspecies variations and no additional 

FQPA safety factors were included in these acute assessments. For the purpose of the 

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

exposure (MOE), which was calculated by dividing the NOAEL by the exposure for each 

population subgroup. In addition, exposure was also expressed as a percent of the 

acute reference dose (%aRfD). Acute (food only) exposure to the U.S. population 

resulted in a MOE of 671 (14.9% of the acute RfD of 0.005 mg/kg-bw/day). The most 

sensitive sub-population was children (1-2 years old) with a MOE of 371 (26.9% of the 

aRfD). Since the benchmark MOE for this assessment was 100 and since the EPA 

generally has no concern for exposures below 100% of the aRfD, Syngenta believes that 

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

exposure to residues arising from the current and proposed uses for abamectin.
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Chronic Exposure. The abamectin chronic dietary (food only) risk assessment was 

performed for all population subgroups with a chronic reference dose of 0.0004 mg/kgbw/day based on combined data from three reproduction studies and two 

developmental neurotoxicity studies with a No Observed Adverse Effect Level (NOAEL) 

of 0.12 mg/kg-bw/day and an uncertainty factor of 300X. The 300-fold safety factor 

includes intra- and interspecies variations (100X) and the additional FQPA safety factors 

of 3X for the steepness of the dose-response curve and the severity of effects. For the 

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

margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure 

for each population subgroup. In addition, exposure was also expressed as a percent of 

the chronic reference dose (%RfD). Chronic (food only) exposure to the U.S. population 

resulted in a MOE of 2,324 (12.9% of the chronic RfD of 0.0004 mg/kg-bw/day). The 

most sensitive sub-population was children (1-2 years old) with a MOE of 672 (44.7% of 

the chronic RfD). Since the benchmark MOE for this assessment was 300 and since the 

EPA generally has no concern for exposures below 100% of the RfD, Syngenta believes 

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

exposure to residues arising from the current and proposed uses for abamectin.

Cancer. Abamectin is considered “not likely to be a human carcinogen”. Therefore, no 

cancer risk assessment was performed for abamectin.

ii. Drinking Water: Another potential source of abamectin exposure to the general 

population is from residues in drinking water. Estimated Drinking Water Concentrations 

(EDWCs) are made by reliance on simulation or modeling taking into account data on 

the physical characteristics and environmental fate of abamectin. For this assessment, 

the uses of abamectin were evaluated by Syngenta using the Tier II model, 

PRZM/EXAMS Shell (PE5), for surface water and the Tier I model SCI-GROW (v 2.3) for 

groundwater.

For surface water the highest EDWCs resulted from the use for dry beans. 

PRZM/EXAMS calculated a surface water acute EDWC of 0.993 ppb and a chronic EDWC 

of 0.358 ppb. For groundwater, the currently registered use for strawberry provided the 

maximum EDWC (acute and chronic) of 0.00229 ppb. Since the surface water EDWCs 

exceed the ground water EDWC, the surface water values should be used for 
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comparison purposes and are considered protective for any ground water concentration 

concerns.

Acute Exposure from Drinking Water. The acute EDWC of 0.993 ppb was used to 

calculate the acute drinking water exposure values for the U.S. Population and 

population subgroups. Acute drinking water exposure to the U.S. population resulted in 

a MOE of 13,514 (0.7% of the aRfD of 0.005 mg/kg/day, Benchmark MOE = 100). The 

most sensitive sub-population was children (1 - 2 years old) with a MOE of 16,667 (0.6% 

of the aRfD of 0.005 mg/kg/day, Benchmark MOE = 100). Since the Benchmark MOE for 

this assessment is 100 and since EPA generally has no concern for exposures below 

100% of the aRfD, Syngenta believes that there is a reasonable certainty that no harm 

will result from acute drinking water exposure to residues arising from the current and 

proposed uses for abamectin.

Chronic Exposure from Drinking Water. The chronic EDWC of 0.358 ppb was used to 

calculate the chronic drinking water exposure values for the U.S. Population and 

population subgroups. Chronic drinking water exposure to the U.S. Population resulted 

in a MOE of 15,903 (Benchmark MOE = 300; 1.9% of the cRfD of 0.0004 mg/kg/day). 

The most sensitive sub-population was infants (<1 year old) with a MOE of 4,851 (6.2% 

of the cRfD of 0.0004 mg/kg/day, Benchmark MOE = 300). Since the Benchmark MOE 

for this assessment is 300 and since EPA generally has no concern for exposures below 

100% of the cRfD, Syngenta believes that there is a reasonable certainty that no harm 

will result from chronic dietary (drinking water) exposure to residues arising from the 

current and proposed uses for abamectin.

2. Non-Dietary Exposure: A residential exposure and risk assessment was performed for 

abamectin using the endpoints and uncertainty factors established by the EPA in a 

recent assessment (March 11, 2009). Residential exposure and risk assessments were 

performed for granular abamectin baits used to treat fire ants on lawns. As such, 

residential assessments included handler exposure for adults and post-application 

exposure risks for adults and children. The highest predicted exposure for adults mixing, 

loading and applying product by belly grinder application to turf resulted in a combined 

(dermal plus inhalation) short-term margin of exposure (MOE) of 112,658. The postapplication dermal exposure to adults following use of granules on lawns is MOE = 

402,379. Children’s post-application dermal plus non-dietary oral aggregate exposure to 
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abamectin from lawn products had a short-term MOE of 48,209. Incidental ingestion of 

granules on treated lawns by children was compared to the acute dietary NOAEL and 

had a MOE of 65,478. 

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”. Unlike other pesticides for which EPA has followed a cumulative risk 

approach based on a common mechanism of toxicity, EPA has not made a common 

mechanism of toxicity finding as to abamectin and any other substances and abamectin 

does not appear to produce a toxic metabolite produced by other substances. Therefore, 

Syngenta has not assumed that abamectin has a common mechanism of toxicity with 

other substances. 

E. Safety Determination

1. U.S. Population. The acute dietary exposure analysis (food plus drinking 

water) showed that exposure from all registered, and proposed abamectin crop uses result 

in a MOE of 639 (15.6% of the aRfD, Benchmark MOE = 100) for the general U.S. 

population. The chronic dietary exposure analysis (food plus drinking water) showed 

that exposure from all registered and proposed abamectin crop uses result in a MOE of 

2,028 (15.0% of the chronic RfD, Benchmark MOE = 300) for the general U.S. 

population. Based on the completeness and reliability of the toxicity data supporting 

these uses, Syngenta believes that there is a reasonable certainty that no harm will result 

from aggregate exposure to residues arising from all current, and proposed abamectin 

uses, including anticipated dietary exposure from food, water, and all other types of nonoccupational exposures. 

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

water) showed that exposure from all registered and proposed abamectin uses results 

in a MOE of 363 (27.5% of the aRfD) for children one to years old (the most sensitive 
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population subgroup). For the short-term aggregate assessments, the children 1-6 years 

old had an aggregate MOE of 757 (Benchmark MOE = 100).The chronic dietary exposure 

analysis (food plus drinking water) showed that exposure from all registered and 

proposed abamectin uses result in a MOE of 632 (47.5% of the cRfD) for children one to 

years old (the most sensitive population subgroup). Since all aggregate MOEs were 

above the Benchmark MOEs and because the EPA has no concern for exposures 

resulting in a MOE above the Benchmark MOE, Syngenta believes that there is a 

reasonable certainty that no harm will result to any population subgroup from 

aggregate exposure to residues arising from all current, and proposed abamectin uses, 

including anticipated dietary exposure from food, drinking water and all other types of 

non-occupational exposures.

F. International Tolerances

Codex has established an abamectin Maximum Residue Level (MRL) of 0.02 

ppm for peppers. The fruiting vegetable tolerance of 0.02 ppm for abamectin is 

harmonized with Codex. International MRLs for abamectin have been established for 

various agricultural commodities in a number of countries including Argentina, Australia, 

Belgium, Brazil, Canada, Czech Republic, Estonia, France, Germany, Greece, Hungary, 

Israel, Italy, Japan, Korea (South), Malaysia, Mexico, Netherlands, New Zealand, Poland, 

Portugal, Russia, , Serbia and Montenegro, Slovak Republic, South Africa, Spain, 

Switzerland, Taiwan, and the United States.