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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING 

EPA Registration Division contact: Laura Nollen, (703) 305-7390

Interregional Research Project Number 4 (IR-4)

Petition Number 0E7738

EPA has received a pesticide petition, PP 0E7738, from 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 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-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1)) and its 

delta-8,9-isomer in or on the raw agricultural commodities onion, bulb, subgroup 3-07A 

at 0.01 parts per million (ppm); chive, fresh leaves at 0.01 ppm; chive, dried leaves at 

0.07 ppm; and bean, dry, seed 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. 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 

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 as required by PR Notice 96–

1.

3. Magnitude of residues. Bulb Onions: Eight residue field trials were conducted 

in California, Colorado, New Mexico, New York, Ohio, Oregon, Texas, and Washington. 

Three foliar applications totaling approximately 0.057 lb ai/A of abamectin were applied 

to the treated plots (except in one California trial, where four foliar applications totaling 

0.076 lb ai/A was applied. . Commercially mature dry bulb onions were collected 

approximately 30 days after the last application. The maximum combined avermectin B1a
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and 8,9-Z avermectin B1a residue from dry bulb onions was 0.0026 ppm in the New York 

trial. In all other samples the residues were below the lowest limit of method validation 

(LLMV). There were no residues of avermectin B1b greater than the LLMV.

Chives: Three residue field trials were conducted in New Jersey, Washington, and 

Maryland. Three foliar applications totaling approximately 0.057 lb abamectin /A was 

applied to the treated plots. . Commercially mature fresh chive leaves were collected 

approximately 6 (±1) days after the last application. At the Washington site, one treated 

and one untreated fresh chive sample was collected 7 days after the final application and 

dried in a drying cabinet for 2 days before collection. An additional fresh chive harvest 

was conducted at the Washington site approximately 13 days after the final application to 

support the possibility of adding chive to the existing tolerance for the Herb crop 

subgroup (except chives).. The maximum combined avermectin B1a and 8,9-Z avermectin 

B1a residue found in the Maryland trial at a 6 ±1 day PHI in fresh chives leaves was 

0.00247 ppm,. Another sample, found in the Washington fresh chives trial, contained a 

combined avermectin B1a and 8,9-Z avermectin B1a residue of 0.00216 ppm. The 

maximum combined avermectin B1a and 8,9-Z avermectin B1a residue from dried chives 

leaves was 0.0101 ppm, found in the Washington trial. In all other samples fresh and dry, 

the residues were below the LLMV. There were no residues of avermectin B1b greater 

than the LLMV.

Dry Beans: Twelve field trials were conducted with dry beans in California, Idaho, 

Washington, Ohio, North Dakota, Wisconsin, and New Jersey. A total of approximately

0.057 lb ai/A of abamectin was applied to the treated plots in three foliar applications. 

Commercially mature dry beans were collected approximately 6 (±1) days after the final 

application. The maximum combined avermectin B1a and 8,9-Z avermectin B1a residue in 

dry beans ,found in a California trial, was 0.004 ppm,. In all other samples the residues 

were below the LLMV. There were no residues of avermectin B1b greater than the 

LLMV.

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
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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)

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 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 
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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’’-O-demethyl 

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.

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.

C. Aggregate Exposure

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

were made for abamectin using the Dietary Exposure Evaluation Model (DEEMFCIDTM, 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, citrus fruit (Crop Group 

10), cotton, cucurbits (Crop Group 9), fruiting 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 
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Group 1C). Section 18 registered uses include bean (lima, seed) and dry bulb onions. 

Abamectin is currently registered for seed treatment (ST) uses on corn, cotton, cucurbits, 

and tomatoes, as a food handling establishment use (Whitmire), a cattle ear-tag use; a 

seed treatment use on soybeans is pending. Proposed uses include an IR-4 foliar uses on 

chives, dry beans (seed), and dry bulb onions. Percent of crop treated values were 

conservatively estimated to be 100% for the proposed use on dry beans. For these 

exposure assessments, residue data were taken from field trial data where 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 660 (15.1% of the acute RfD of 0.005 mg/kg-bw/day). The most sensitive subpopulation was children (1-2 years old) with a MOE of 367 (27.2% 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.

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/kgbw/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 2,344 (12.8% 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 677 (44.3% of 

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

proposed uses of abamectin on bulb onion, beans (dry) and chives, as well as all existing 

uses were evaluated using the Tier 2 Model, PRZM/EXAMS Shell (PE5) for surface 

water and the Tier 1 model SCI-GROW (v 2.3) for groundwater.

For surface water the highest EDWCs resulted from the proposed 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 ground water the currently registered use for cucurbits 

provided higher EDWCs than the proposed uses. For the groundwater model, the 

cucurbits application parameters consisted of one seed treatment at 0.066 lb a.i./A 

(adjusted for 6% desorption from seed) followed by three aerial applications at 0.019 lb 

a.i./A with application intervals of 7 days. This provided an EDWC (acute and chronic) 

of 0.00184 ppb.

Since the surface water EDWCs exceed the ground water EDWC, the surface water 

values should be used for 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 

25,000 (0.4% of the aRfD of 0.005 mg/kg/day, Benchmark MOE = 100). The most 

sensitive sub-population was children (3 - 5 years old) with a MOE of 20,833 (0.5% 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 15,000 (Benchmark MOE = 300; 2.0% of the cRfD of 0.0004 mg/kg/day). 

The most sensitive sub-population was infants (<1 year old) with a MOE of 5,000 (6.0% 

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 
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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 lawns and for indoor abamectin-based crack 

and crevice products. 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 60,550. The post-application dermal exposure to adults following use of 

granules on lawns is MOE = 402,379. Children’s post-application dermal plus nondietary oral aggregate exposure to abamectin from lawn products had a short-term MOE 

of 48,192. Incidental ingestion of granules on treated lawns by children was compared to 

the acute dietary NOAEL and had a MOE of 65,563. The highest predicted exposure for 

adults applying dust to crack and crevices resulted in a combined (dermal plus inhalation) 

short-term MOE of 1,976,285. The post-application dermal exposure to adults following 

use of a dust formulation had a MOE of 1,796,407. Post-application dermal plus nondietary oral exposure from abamectin use in dust products are acceptable (short-term 

aggregate MOE = 288,462, intermediate-term aggregate MOE = 483,871) for children reentering indoor carpeted areas following crack and crevice treatments. Other 

formulations for similar crack and crevice products are expected to have less migration 

from the treated area and thus, to result in lower risk from dermal, oral, and inhalation 

post application exposure. The MOEs for all residential scenarios for children do not 

exceed the EPA’s level of concern (Benchmark MOE of 300) and there is a reasonable 

certainty that no harm will result from the residential uses of abamectin.

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 
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in a MOE of 643 (15.5% 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 

2,043 (14.7% 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 petitions, 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 non-occupational exposures. 

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

water) showed that exposure from all registered and proposed abamectin uses result in a 

MOE of 363 (27.5% of the aRfD) for children one to years old (the most sensitive 

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

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

637 (47.1% 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.