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EPA REGISTRATION DIVISION COMP ANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: Thomas C. Harris 703-308-9423

Syngenta Crop Protection, LLC

PP # 3F8184

EPA has received a pesticide petition PP # 3F8184 from Syngenta Crop Protection, LLC, PO 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

1. by establishing a tolerance for residues of

abamectin in or on the raw agricultural commodity corn, field, sweet and

pop at 0.01 ppm; soybean at 0.01 ppm; corn, field and pop, forage at 0.2 ppm; corn, field and pop, grain at 0.01 ppm; co rn, field and pop, st over at 0.6 ppm; corn, sweet, forage at 0.2 ppm; corn, sw eet, kernel plus cob with husk removed at 0.01 ppm; corn, sweet, stover at 0.5 ppm; soybean forage at 0.3 ppm; soybean, hay at 1 ppm; and soybean, seed at 0.01 parts per million (ppm). EPA has determined that the pet ition 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 t he submitted data at this time or whether the data supports granting of the petition. A dditional 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 in clude the parent insecticide abamectin (also referred to as avermectin B 1 which is a mixture of a minimum of 80%

avermectin B 1a and a maximum of 20% avermectin B 1b ) and the delta 8,9-isomer

of the B 1a and of the B 1b components of the par ent insecticide.

2. Analytical method. The analytical methods involve homogenization, filtration, partition, and cleanup with anal ysis by high performance liquid chromatography (HPLC)-fluorescence det ection. The methods are sufficiently

sensitive to detect residues at or abov e the tolerances proposed. All methods have undergone independent laboratory validation.

A. 3. Magnitude of residues.2

Results of MOR Studies with the Abamectin on Soybean

Twenty crop-field trials were successfu lly conducted in the United States to support the registration of abamectin on so ybeans resulting from a combination of a seed treatment application with A bamectin 500 FS (A14006B), a flowable concentrate for seed treatment (FS) formu lation, and two foliar applications of Abamectin SC (A15368D), a suspension concentrate (SC) formulation. The seed treatment application was made at a nominal rate of 0.15 mg ai/seed, and the two foliar applications were made at the maximum proposed label use rate of 0.019 lb ai/A/application. At each si te, one treated plot was established for forage and hay sample collection with folia r applications made nominally 14 ± 1 and 7 ± 1 days before forage harvest and cu tting of hay. At each site, another treated plot was established for seed samp le collection with foliar applications made nominally 35 ± 1 and 28 ± 1 days before seed harvest. The foliar applications included an adj uvant [non-ionic surfact ant (NIS) or crop oil concentrate (COC)] in the spray solutions as specified for each site following the

manufacturer’s recommended label rate. At two sites, another treated plot was

established that was treated in the sa me manner and timing as described above for seed harvest, but at a 5× rate (0.095 lb ai/A/application) to produce seed for processing into aspirated grain frac tions (AGF), meal, hulls, and refinedbleached-deodorized (R BD) oil.

Forage samples were collected and hay sa mples cut 7 ± 1 days after the last application (DALA) during the blooming per iod. The hay samples were allowed to dry to ~80-90% dry matte r prior to collection. Seed samples were collected 28 ± 1 DALA at normal crop maturity. At two trial sites, additional RAC samples were collected (1, 3, 10, and 14 DALA for forage and hay; 20-21, 23-24, 31-32, and 34-35 DALA for seed) to generate residue decline data.

Residues of abamectin, a mixture containi ng avermectin B1a (parent B1a + 8,9-Z B1a) and avermectin B1b, were determined in or on all of the collected soybean forage, hay, seed, AGF, meal, hulls, and RBD oil samples. The fortification levels were 0.002 (LOQ), 0.0336, and 3. 36 ppm for B1a, and 0.002 (LOQ) and 0.20 ppm for B1b and 8,9-Z isomer.

Residues above the LOQ were not f ound in any of the non-treated control samples of any soybean matrix except for two hay samples with residues just above the LOQ (0.00246 ppm from Trial -15 and 0.00202 ppm from Trial -20) and one AGF sample (0.00320 ppm from Trial -20).

Results of MOR Studies with the Abam ectin in Field Corn and Popcorn

Twenty crop-field trials on field corn and three crop-field trials on popcorn were successfully conducted in the United St ates to support the registration of abamectin on field corn and popcorn result ing from a combination of a seed3

treatment application with Abamectin 500 FS (A14006B), a flowable concentrate for seed treatment (FS) formulation, and two foliar applications of Abamectin SC (A15368D), a suspension concentrate (SC) formulation. The seed treatment application was made at a nominal rate of 0.25 mg ai/seed, and the two foliar applications were made at the maximum proposed label use rate of 0.019 lb ai/A/application. At each field corn site, one treated plot was established for forage sample collection with foliar applic ations made nominally 14 ± 1 and 7 ± 1 days before field corn forage harvest. At each field corn and each popcorn site, another treated plot was established for grain and stover sample collection with foliar applications made nominally 28 ± 1 and 21 ± 1 days before grain/stover harvest. The foliar applications included an adjuvant [non-ioni c surfactant (NIS) or crop oil concentrate (COC)] in the sp ray solutions as specified for each site following the manufacturer’s recommended label rate. At two field corn sites, another treated plot was established that was treated in the same manner and timing as described above for grain har vest, but at a 5× rate (0.095 lb ai/A/application) to produce grain for generation of aspirated grain fractions (AGF) and for processing into grits, meal, flour, and refined-bleached-deodorized (RBD) oil from dry milling, and starch and RBD oil from we t milling.

Field corn forage (with ears) samples we re collected nominally 7 ± 1 days after the last application (DALA) at the late dough to early dent stage. Field corn and popcorn grain and stover samples were collected nominally 21 ± 1 DALA at normal crop maturity. At two field corn trial sites, additional RAC samples were collected (1, 3, 10, and 14 DALA for fo rage; 14, 17-18, 24-25, and 27-28 DALA for grain and stover) to generate residue decline data.

Residues of abamectin, a mixture containi ng avermectin B1a (parent B1a + 8,9-Z B1a) and avermectin B1b, were determined in or on all of the collected field corn forage, grain, stover, AGF, grits, meal, flour, RBD oil (dry milling and wet milling) and starch samples and all of the collected popcorn gr ain and stover samples. The abamectin method of analysis was verified on field corn forage, grain, stover, meal, flour, grits, starch, and refined oil (dry milling) prior to field sample analysis. The fortification levels were 0.002 (L OQ), 0.0336, and 3.36 ppm for B1a, and 0.002 (LOQ) and 0.20 ppm for B1b and 8,9-Z isomer. The overall mean recoveries for all analytes in all matrices ranged 71-111% and the relative standard deviations (RSD) ranged 5.8-22% (all ≤ 20% except for B1b in grain).

Concurrent procedural recovery sample s were analyzed in conjunction with each analytical set for quality control purposes. The overall mean recoveries for all analytes in all matrices ranged 61-112% (within 60-120%) and the relative standard deviations (RSD) ranged 5.3-28% (all ≤ 20% except for B1a in popcorn stover).4

Residues above the LOQ were not f ound in any of the non-treated control samples of any field corn or popcorn ma trix except for one forage sample with avermectin B1a residues of 0.00409 ppm. When this sample was reanalyzed, residues were ND; therefore, the initial residues in the control sample appear to be laboratory contamination.

Results of MOR Studies with the Abamectin in Sweet Corn

Twelve crop-field trials were successf ully conducted in the United States to support the registration of abamectin on sweet corn resulting from a combination of a seed treatment application with A bamectin 500 FS (A14006B), a flowable concentrate for seed treatment (FS) formu lation, and two foliar applications of Abamectin SC (A15368D), a suspension concentrate (SC) formulation. The seed treatment application was made at a nominal rate of 0.25 mg ai/seed, and the two foliar applications were made at the maximum proposed label use rate of 0.019 lb ai/A/application. The two foliar applications were made 14 ± 1 and 7 ± 1 days before fresh market harvest of fo rage and kernel + cob with husk removed (K+CWHR) and cutting of the stover samples. The foliar applications included an adjuvant [non-ionic surfactant (NIS) or crop oil concentr ate (COC)] in the spray solutions as specified for each site following the manufacturer’s recommended

label rate.

Forage and K+CWHR samples were harvested 7 ± 1 days after the last application (DALA). The stover samples were cut 7 DALA and allowed to dry to ~80-85% dry matter. At two trial sites, additional RAC samples were collected (1, 3, 10, and 14 DALA) to gener ate residue decline data.

Residues of abamectin, a mixture containi ng avermectin B1a (parent B1a + 8,9-Z B1a) and avermectin B1b, were determined in or on all of the collected sweet corn forage, K+CWHR, and stover sample s. The abamectin method of analysis was verified on sweet corn forage, K+CW HR, and stover prior to field sample analysis. The fortification levels we re 0.002 (LOQ), 0.0336, and 3.36 ppm for B1a, and 0.002 (LOQ) and 0.20 ppm for B1b and 8,9-Z isomer. The mean recoveries for all analytes in all matrices ranged 78-100% and the relative standard deviations (RSD) ranged 10-23% (all <20% except for 8,9-Z in

K+CWHR and stover ).

Concurrent procedural recovery samples were analyzed in conjunction with each analytical set for quality control purposes. The mean recoveries for all analytes in all matrices ranged 72-100% (withi n 70-120%), and the relative standard deviations (RSD) ranged 10-18% (all <20%).

Residues above the LOQ were not f ound in any of the non-treated control samples of any sweet corn matrix.5

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 LD 50 of 13.6 mg/kg. ii. A rat acute oral study with an LD 50 of 214-232 mg/kg. iii. A rabbit acute dermal study with an LD 50 of 2000 mg/kg. iv. A rat acute inhalation study with an LC 50 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 r abbits which showed slight irritation. vii. A dermal sensitization study (Buehle r) in guinea pigs which was negative.

Abamectin Technical II

i. A rat acute oral study with an LD 50 of 372.5 mg/kg ii. A rat acute dermal study with an LD 50 of >200 mg/kg but <2000 mg/kg ii. A rat acute inhalation study with an LC 50 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 r abbits which showed slight irritation. vii. A dermal sensitization study (B uehler) in guinea pigs with Abamectin Technical supports the regist ration 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 acti vation did not produce mutations. In an alkaline elution/rat hepatocyte assay, abamectin was found to induce single strand DNA breaks without significant to xicity in rat hepatocytes treated in vitro at doses greater than 0.2 millim ole 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. Ther e are also, many studies and a great deal of clinical and follow-up experienc e 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 mort ality. 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 maternal6

NOAEL was 1.0 mg/kg/day based upon dec reased 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 developmenta l toxicity study the maternal NOAEL in CF-1 mice that expressed P-glycopr otein was greater t han 1.5 mg/kg/day, the highest and only dose tested. No cleft palat es 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 mater nal 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 wei ght loss. In a second developmental neurotoxicity study in rats the mater nal 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 weig ht 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 wit h 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 carcinoge nicity feeding study was negative for carcinogenicity, with a NOAEL of 4 mg/kg/day based upon decreased body weights. A dog 53–week chr onic 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 derivat ive 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 metabo lites was evaluated in toxicology studies with abamectin photol ytic break-down product, the delta 8,9-

isomer.7

8. Endocrine disruption

. There is no evidence that abamectin is an endocrine disrupter. Evaluation of the rat multigeneratio nal 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 behav ior, 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 subchroni c toxicity studies in mice, rats, and dogs did not demonstrate any evidence of toxicity to the male or female reproductive tract, or to the thyroi d or pituitary (based upon organ weights and gross and histopathologic examination). In the developmental studies, the pattern of toxicity observed does not seem s uggestive of any endocrine effect. Finally, experience with ivermectin in breeding anim als, including sperm evaluations in multiple species, shows no adverse effect s suggestive of endocri ne 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 Agen cy was initiating the Endocrine Disruptor Screening Program for these compounds. In 2010 t he EPA issued Data-Call In’s the endocrine assays required for specified acti ve ingredients including abamectin. The Abamectin EDSP Consortium is generating the required assays

C. Aggregate Exposure

1. Dietary exposure. Tier III/IV acute, shor t-term, and chronic aggregate exposure evaluations were made for abamectin using the Dietary Exposure

Evaluation Model software with the Food Commodity Intake Database (DEEMFCID TM , version 3.14), which incorporates food consumption data from the

National Health and Nutrition Examinati on Survey/“What We Eat in America” (NHANES/WWEIA) dietary survey conduc ted in 2003-2008. These assessments included all current foliar, food handli ng establishment (FHE), and residential uses for abamectin, pending uses on cotton and strawberries, and a proposed new IR-4 use on caneberries (Crop Gr oup 13-07A). For these exposure assessments, residue data were taken from field trial residue studies in which abamectin was applied at the maximum intended use rate and samples were harvested at the minimum pre-harvest in terval (PHI) to obtain maximum residue values. Drinking water esti mates were incorporated directly into the dietary exposure assessment using the higher of the estimated drinking water concentrations (EDWCs) for surface and ground water. Percent crop treated values were estimated based upon economic , pest, and competitive pressures.

Residue values for milk and livestock co mmodities were obtained from the EPA’s July 18, 2011 abamectin dietar y risk assessment (D380796).

i. Food. Acute Exposure. The abamecti n acute dietary (food only) risk assessment was performed for all populat ion subgroups with an acute reference dose of 0.005 mg/kg-bw/day based on a 12-week dose-range finding study in8

dogs with a No Observed Adverse Effect Level (NOAEL) of 0.5 mg/kg-bw/day and an uncertainty factor of 100X. The 100-fo ld safety factor includes intra- and interspecies variations and no additional FQ PA safety factors were included in

these acute assessments. For the purpose of the aggregate risk assessment, exposure values were expr essed 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 onl y) exposure to the U.S. population resulted in a MOE of 719 ( 13.9% of the acute RfD of 0.005 mg/kg-bw/day). The most sensitive sub-populat ion was children (1-2 year s old) with a MOE of 376 (26.6% of the aRfD). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concer n for exposures above the benchmark or below 100% of the reference dose, Syngenta believes that there is a reasonable certainty that no harm will resu lt from acute food exposure to residues arising from all current, pendi ng, and proposed uses for abamectin.

Chronic Exposure. The abamectin chr onic dietary (food only) risk assessment was performed for all population subgroups with a chronic reference dose of 0.0004 mg/kg-bw/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 expresse d in terms of margin of exposure (MOE), which was calculated by dividi ng the NOAEL by the exposure for each population subgroup. In additi on, exposure was also expressed as a percent of the chronic reference dose (%RfD). Ch ronic (food only) exposure to the U.S. population resulted in a MOE of 2,936 ( 10.2% of the chr onic RfD of 0.0004 mg/kg-bw/day). The most sensitive sub- population was childr en (1-2 years old) with a MOE of 669 (44.8% of the chronic RfD). Sinc e the Benchmark MOE for this assessment was 300 and since the EPA generally has no concern for exposures above the benchmark or below 100% of the reference dose, Syngenta

believes that there is a reasonable certai nty that no harm will result from chronic food exposure to residues arising fr om all current, pending, and proposed uses

for abamectin.

ii. Drinking water. The Estimated Drinking Wa ter Concentrations (EDWCs) of abamectin were determined using Tier 1SCI-GROW which es timates pesticide concentration in ground water and Tier 2 PRZM/EXAMS which estimates pesticide concentration in surface wate r. EDWCs of abamectin from the currently registered and pending uses as well as a proposed use on caneberries were determined using EPA’s model inputs. Based on the SCI-GROW modeling, the highest groundwater EDWC for abamectin is 0.00188 ppb (acute and chronic) based on the currently register ed/pending use on strawberries. Based on the PRZM/EXAMS modeling, the curr ently registered use on dry beans9

provided the highest surface water ED WCs of 2.35 ppb for acute and 1.39 ppb

for chronic. Since the surface wa ter EDWCs exceed the ground water EDWC,

the surface water values were used fo r risk assessment purposes and will be considered protective for any gr ound water exposure concerns.

Acute Exposure from Drinking Water. The acute surface water EDWC of 2.35 ppb was incorporated directly into the DEEM software as “water, direct and indirect, all sources” to model the acut e drinking water exposures by taking the difference between the aggregate (food + dr inking water) exposures and the food (alone) exposures for each population subgr oup at the 99.9%-ile of exposures. Acute drinking water exposure to the U.S. population resulted in a MOE of 4,808 (2.1% of the acute RfD of 0.005 mg/k g-bw/day). The most exposed subpopulation was all infants (<1 year old) with a MOE of 3, 106 (3.2% of the aRfD of 0.005 mg/kg/day). Since the Benchmar k MOE for this assessment was 100 and since the EPA generally has no concern fo r exposures above the benchmark or below 100% of the reference dose, Syngent a believes that there is a reasonable certainty that no harm will result from ac ute drinking water exposure to residues arising from all current, pending, and proposed uses for abamectin.

Chronic Exposure from Drinking Water. The chronic surface water EDWC of 1.271 ppb was input directly into the D EEM software as “water, direct and indirect, all sources” to model the ch ronic drinking water exposures. Chronic drinking water exposure to the U.S. populat ion resulted in a MOE of 4,123 (7.3% of the chronic RfD of 0.0004 mg/kg-bw/day ). Chronic drinking water exposure to the most exposed sub-population (infants, <1 year old) resulted in a MOE of 1,599 (18.8% of the chroni c RfD of 0.0004 mg/kg-bw/day ). Since the Benchmark MOE for this assessment was 300 and since the EPA generally has no concern for exposures above the benchmark or below 100% of the reference dose, Syngenta believes that there is a reasonab le certainty that no harm will result from chronic drinking water exposure to residues arising from all current, pending, and proposed uses for abamectin.

2. Non-dietary exposure

. Residential exposure risk assessments were performed for use of abamectin formula ted as Varsity® Fire Ant Bait and Optigard® Fire Ant Bait for residential turf. Residential a dult handler/applicator assessments were performed fo r activities including push spreader, belly grinder, spoon, cup, hand dispersal, and shaker can. Residential post-application exposure scenarios assessed included adult and child high contact dermal, adult and youth mower, adult and youth golfer, and child hand-to-mouth, object-tomouth, soil ingestion, and ingestion of granules. The most-exposed adult (19+ years) handler/applicator scenario was for belly-grinder applications, with a shortterm MOE of 899,348 (Benchmark = 300). The most-exposed youth (11-16 years) post-application scenario was for t he youth golfer, with a short-term MOE of 15,753,170 (Benchmark = 300). The mo st-exposed youth (6-11 years) postapplication scenario was for the youth golfer, with a short-term MOE of 13,418,308 (Benchmark = 300). The most-exposed childr en’s (1-6 years) post-10

application scenario was vi a hand-to-mouth and dermal exposures resulting from play activities on treated turf, with a combined short-term MOE of 343,564 (Benchmark = 300). Incidental oral ingesti on of granules by children had a shortterm MOE of 48,017 (Benchmar k = 300; granule ingestion is not aggregated with other exposure scenarios).

D. Cumulative Effects

Cumulative Exposure to Substanc es with a Common Mechanism of Toxicity. Section 408(b)(2)(D)(v) requi res that, when considering whether to establish, modify, or revoke a tole rance, the Agency consider “available information” concerning the cumulative effe cts of a particular pesticide’s residues

and “other substances that have a common mechanism of toxicity”. If, in the future, EPA obtains new data suggesti ng that abamectin shares a common mechanism of toxicity with other chemical substances, the Agency will revisit the

need for a cumulative risk a ssessment. For the purposes of this filing, Syngenta

has not assumed that abamectin has a co mmon 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 current, pending, and proposed abamectin crop uses result in a MOE of 625 (16. 0% of the aRfD, Benchmark MOE = 100) for the general U.S. populat ion. The short-term ex posure analysis (food plus drinking water plus residential) showed t hat exposure from all current, pending, and proposed abamectin uses result in a MOE of 1,711 (Benchm ark MOE = 300) for the general U.S. populati on. The chronic dietary exposure analysis (food plus drinking water) showed that exposure fr om all current, pending, and proposed abamectin crop uses result in a MOE of 1,715 (17.5% of the chronic RfD, Benchmark MOE = 300) for the gener al U.S. population. Based on the completeness and reliability of the toxici ty data supporting these uses, Syngenta

believes that there is a reasonable certai nty that no harm will result to the general U.S. population from aggregate exposure to residues arising from all current, pending, and proposed abamectin uses, in cluding anticipated dietary exposure from food, water, and all ot her types of non-occupational residential exposures.

2. Infants and children

. The acute dietary exposure analysis (food plus drinking water) showed that exposure from all current, pending, and proposed abamectin uses results in a MOE of 342 ( 29.2% of the aRfD) for children 1-2 years old (the most sensitive populati on subgroup). For the short-term aggregate assessments, children 1-2 years old had an aggregate MOE of 542 (Benchmark MOE = 300) for all current, pending, and proposed abamectin uses. The chronic dietary exposure analysis (food plus drin king water) showed that exposure from all current, pending, and proposed abamecti n uses result in a MOE of 542 (55.3% of the cRfD) for children 1-2 y ears old (the most sensitive population11

subgroup). Based on the completeness and reliability of the toxicity data supporting these uses, Syngenta believes t hat there is a r easonable certainty

that no harm will result to infants and children from aggregate exposure to residues arising from all curren t, pending, and proposed abamectin uses, including anticipated dietary exposure fr om food, water, and all other types of non-occupational resident ial exposures.

F. International Tolerances

Codex has established Maximum Resid ue Levels (MRLs) for abamectin on a

number of commodities incl uding almonds, apples, citr us, cotton, cucumbers, hops, lettuce, meat, milk, and related commodities (beef and goat), melons, pears, peppers, potatoes, squash, strawber ries, tomatoes, and walnuts. In addition, country or region-specific inte rnational MRLs for abamectin have been established or proposed in a number of c ountries including: Argentina, Australia, Brazil, Canada, Chile, Ch ina, France, Germany, Greec e, Hungary, Italy, Japan, Korea, Mexico, Russia, South Africa, S pain, Switzerland, Taiwan, Turkey, United Kingdom, and the United States.