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

Interregional Research Project Number 4 (IR-4) Petition Number (PP#) 2E8029 EPA has received a pesticide petition , PP# 2E8029, from Interregional Research Proje ct Number 4 (IR- 4), IR- 4 Project Headquarters, Rutgers, The State University o f New Jersey, 500 College Road East, Suite 201 W, Princeton, NJ 0 8450 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 .564 by

establishing a tolerance for residues of the combined residues of I ndoxacarb, (S) -methy

l 7 - chloro - 2,5 - dihy

dro - 2 - [[(methoxy

carbony l)[4 - (trifluoromethoxy

)pheny l]amino]carbony

l] - indeno[1,2e ] - [1,3,4 ]oxadiazine -4a(3H) - carboxy late and its R- enantiomer (R) -methy l - 7 - chloro - 2,5 - dihy dro - 2 - [[(methoxy

carbony l)[4 - (trifluoromethoxy

)pheny l]amino]carbony

l] - indeno [1,2 - e] [1,3,4] oxadiazine -4a(3H) - carboxy late in a 75:25 mixture (DPX- MP062), respectively, in or on the raw agricult ural commodity bean , dry, seed at 0.07 p arts per million (ppm); bean, succulent at 0.64 ppm ; bean, forage ( foliage of leguminous vegetables/cow pea foliage ) at 37 ppm ; small fruit , vine climbing, except fuzzy kiwifruit, subgroup 13 - 07F at 2.0 ppm ; and berr y, low growing, except strawberry, subgroup 13 - 07H at 0.9 ppm . Upon approval of the aforementioned tolerances, the petition additionally

requests to remove the established tolerances in or on grape at 2.0 ppm and cranberry a t 0.90 ppm. in EPA has determine d that the petition contains data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency

o f the submitted data at this time or whether the data supports granting of the petiti on. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry The active ingredient in the end-use formulation DuPont Avaunt® In secticide is a 75:25 mixture of two isomers, indoxacarb (DPX - KN128) and IN - KN127 . Only one of the isomers, indoxacarb (DPX - KN128), has insecticidal activity . The active ingredient in the end-use formulation, DuPontTM Steward® EC In secticide is indoxacarb; no IN - KN127 is present. S ince the insecticidal efficacy

i s based on the concentration of indoxacarb (DPX - KN128), the application rates have been normalized on an indoxacarb (DPX - KN128) basis. The proposed tolerance expression includes both indoxacarb (DPX - KN128) and IN - KN127 and the residue method does not distinguish between the enantiomers, therefore residues are reported as the sum of indoxacarb (DPX - KN128) combined with I N - KN127. Residues of indoxacarb (DPX - KN128) combined with IN - KN127 will be referred to as "KN128/KN127." 1. Plant metabolism . The metabolism of indoxacarb in plants is adequately

understood to support these tolerances. Plant metabolism studies in cotton, lettuce, and tomatoes showed no significant metabolites. The only s ignificant residue was parent compound. 2. Analytical method . The plant residue enforcement method2

detects and quantitates indoxacarb in various matrices including sweet corn, lettuce, tomato, broccoli, apple, grape, cottonseed, tomato, peanut and soy bean commodity

s amples by

HP LC UV. The limit of quantitation in the method allows monitoring of crops with indoxacarb residues at or above the levels proposed in these tolerances. 3. Magnitude of residues. Nine field trials were conducted on snap bean s . Each field trial site consisted of one untreated control plot and one treated plot. At all the trials the test substance was applied as a foliar application. Four applications, six to eight days apart, were made at the maximum use rate of 0. 11 9 lb of indoxacarb active ingredient per acre (0. 45 7 lb of active ingredient maximum seasonal use rate). H arvesting was done 2 - 3, 7 and 13 days after the last application. For the pods with seeds samples (at the 2

– 3 day P HI), the residue levels ranged from 0.04 to 0.59 ppm and for the plant samples (at the 2

– 3 day PHI), the residue levels range from 1.3 to 32.1 ppm . Thirteen field trials were conducted on dry beans. E ach field trial site consisted of one untreated control plot and one treated plot. At all the trials the test substance was applied as a foliar application. F our applications, six to eight days apart, were made at 0.106 to 0.118 lb of indoxacarb active ingredient per acre (0.438 to 0.463 lb of active ingredient maximum seasonal use rate). H arvesting was done 6 - 8 days after the last application. The residue levels in the harvested beans ranged from < 0.01 ppm to 0.093 ppm. B. Toxicological Profile

1. Acute toxicity . Based on EPA criteria, indoxacarb is cl assified as follows for Toxicity Categories Guideline Title Results Category 870.1100 870.1200 870.1300 870.2400 870.2500 Acute Oral Toxicity

Acute Dermal Toxicity Acute Inhalation Toxicity Primary Eye I rritation Primary Dermal Irritation Skin Sensitization LD50:1730 mg/kg (M Rat) LD50: 268 mg/kg/(F Rat) LD50: >5000 mg/kg (Rat) LC 50: >5.5 mg/L(M Rat) (70% MUP) Effects reversed within 72 hours (Rabbit) No irritation (Rabbit) Category II Category IV Category I V Category III Category I V3

870.2600 Sensitizer (Guinea Pig) --------------- Formulated products are slightly less acutely

toxic than indoxacarb. Inan acute neurotoxicity

study, indoxacarb exhibited decreased forelimb grip strength, decreased foot splay, and some evidence of slightly reduced motor activity, but only at the highest doses tested. The NOAEL was 100 mg/kg for males and 12.5 mg/kg for females based on body weight effects in females  50 mg/kg.]

2. Genotoxicty . [I

ndoxacarb has shown no genotoxic activity in the following listed in-vitro and in-vivo tests:

Ames -- Negative In-vitro mammalian gene mutation (CHO/HGPRT) -- Negative In-vitro unscheduled DNA sy nthesis -- Negative In-vitro chromosomal aberration-- Negative In-vivo mouse micronucleus -- Negative] 3. Reproductive and developmental toxicity . The results of a series of studies indicated that there were no reproductive, developmental or teratogenic hazards associated with the use of indoxacarb. In a 2 - generation rat reproduction study, the parental NOAEL was 1.5 mg/kg/day. The parental NOAEL was based on observations of reduced weight gain and food consumption for the higher concentration groups of the F0 generation and potential treatment-related changes in spleen weights for the higher groups of the F1 generation. There was no effect on mating or fertility. The NOAEL for fertility a nd reproduction was 6.4 mg/kg/day. The offspring NOAEL was 1.5 mg/kg/day, and was based on the reduced mean pup weights noted for the F1 litters of the higher concentration groups. The effects on pup weights occurred only a t a maternal effect level and may have been due to altered growth and nutrition in the dams. In studies conducted to evalua

te developmental toxicity p otential, indoxacarb was neither teratogenic nor uniquely toxic to the conceptus (i.e., not considered a developmental toxin). Developmental studies conducted in rats and rabbits demonstrated that the rat was more susceptible tha n the rabbit to the maternal and fetal effects of DPX- MP062. Developmental toxicity was observed only

in the presence of maternal toxicity. The NOAEL for maternal and fetal effects in rats was 2 mg/kg/day based on body

weight effects and decreased food consumption at 4 mg/kg/day. The NOAEL for developmental effects in fetuses was >4 mg/kg/day. In rabbits, the maternal and fetal NOAELS were 500 mg/kg/day

b ased on body

weight effects, decreased food consumption in dams and decreased weight and delayed ossifi cation in fetuses at 1000 mg/kg/day.

Ina developmental neurotoxicity s tudy, dams administered 3 mg/kg/day f rom gestation day

6through lactation day 1 0 had decreased body w eight, weight gain, and food consumption; increased incidences of clinical signs of toxicity ; and test substance -related mortality . At maternally toxic doses of 3 mg/kg/day, there was also an increase in offspring4

effects including lower body weight. In addition, beginning on lactation day 11, offspring were directly administered the test substance daily by oral gavage through lactation day 2 1. There were no effects in offspring on learning and memory, sexual maturation, motor activity, acoustic startle habituation, terminal body w eights, brain weights, selected hematology p arameters, neuromorphometric parameters, or neurohistopathology . There were no biologically s ignificant effects on dams or offspring administered dosages of 1.5, 1, or 0.5 mg/kg/day.

4. Subchronic toxicity . Subchronic (90 - day ) feeding studies were conducted with rats, mice, and dogs. In

a 90 - day f eeding study

in rats, the NOAEL

was 3.1 and 2.1 mg/kg/day for males and females, respectively. In male rats, the NOAEL was based on decreased body weight and nutritional parameters, mild hemoly tic anemia and decreased total protein and globulin concentration. I

n female rats, the NOAEL was based on decreased body weight and food efficiency. In a subchronic neurotoxicity study in rats, there was no evidence of neurotoxicity a t 11.9 and 6.09 mg/kg/day, the highest dose tested for males and females, respectively. The subchronic NOAEL in dogs (5.0 mg/kg/day, M/F) was based on hemoly tic anemia. Ery

throcy te values for most dogs were within a range that would be considered normal for dogs in a clinical setting. Mice were less sensitive to indoxacarb than the rats or dogs. NOAELs (23 mg/kg/day, males, 16 mg/kg/day, females) were based on mortality (males only

); increased reticulocy

tes and Heinz bodies and decreased body

weight, weight gain, food consumption, food efficiency; and increased clinical signs (leaning to one side and/or with abnormal gait or mobility ) (females only

). In a 2 8 - day repeated dose dermal study, the NOAEL was 50 mg/kg/day

based on decreased body

weights, body weight gains, food consumption, and food efficiency in females, and changes in hematology parameters, the spleen and clinical signs of toxicity in both sexes in rats. ] 5. Chronic toxicity . Chronic studies with indoxacarb were conducted on rats, mice, and dogs to determine oncogenic potential and/or chronic toxicity o f the compound. Effects generally similar to those observed in the 90 - day studies were seen in the chronic studies. I ndoxacarb was not oncogenic in rats or mice. The chronic NOAEL in male rats was 5 mg/kg/day based on body

weight and nutritional effects. In f emales, the NOAEL of 2.1 mg/kg/day was based on body

weight and nutritional changes, as well as biologically s ignificant hematologic changes at 3.6 mg/kg/day a nd above. Hemoly

tic effects were present only t hrough the 6 -month evaluation and only in females. The regenerative nature of indoxacarb - induced hemoly tic anemia was demonstrated by t he absence of significant changes in indicators of circulating ery throcy te mass at later evaluations. In mice, the chronic NOAEL of 2.6 mg/kg/day f or males was based on deceased body weight and weight gain effects and food efficiency a t 13.8 mg/kg/day

a nd above. The NOAEL for females was 4.0 mg/kg/day

b ased on body

weight nutritional effects , neurotoxicity, and clinical signs at 20 mg/kg/day. In

dogs, the chronic NOAEL was about 2.3 and 2.4 mg/kg/day in males and females, respectively

based on hemoly

tic effects similar to those seen in the subchronic dog study.5 6. Animal metabolism . Livestock animal metabolism. Animal metabolism has been studied in the rat, hen, and cow and is well understood. In c ontrast to crops, indoxacarb is extensively

metabolized in animals. Poultry. In

p oultry, hens were fed at 10 ppm/day f or 5 days, 87 - 88% of the total administered dose was excreted; parent comprised 51 - 54% of the total dose in excreta. Concentrations of residues in eggs were low, 0.3 - 0.4 of the total dose, as were the concentrations of residues in muscle, 0.2% of t he total dose. Parent and metabolite IN- JT333 were not detected in egg whites; only insecticidally inactive metabolites were identified. Parent and IN- JT333 were found in egg yo lks; however, their concentrations were very l ow- 0.01 - 0.02 ppm. Concentrations of parent and IN- JT333 in muscle were at or below the limit of quantitation, (LOQ) (0.01 ppm). Poultry F eeding study. F our groups of lay ing hens (10/ group) were dosed orally once a day

f or 28 consecutive days -with capsules containing indoxacarb at leve ls equivalent to target concentrations of 1.75, 7.0, 21.0, and 70.0 ppm in the feed on a dry weight basis. Residues of each analy te plateaued in whole eggs within 14 - 21 days of dosing. Residues in fat, skin, and liver were dose dependent, particularly

for the top three dose levels. The maximum combined residues in fat were 0.11, 0.54, 1.5, and 5.0 ppm from the 1.75, 7, 21, and 70 ppm dose groups, respectively; and combined residues in fat averaged 0.10, 0.44, 1.4, and 4.13 ppm from the respective dose groups. The maximum combined residues inskin were <0.07,0.17,0.60, and 1.20 ppm from the 1.75,7,21, and 70 ppm dose groups, respectively; and combined residues in skin averaged <0.07,0.12,0.51, and 1.06 ppm from the respective dose groups. In liver, the maximum combined residues were <0.06, <0.09, 6.21, and 0.67 ppm from the 1.75,7,21, and 70 ppm dose groups, respectively; and combined residues in liver averaged 0.03, 0.08, 0.18, and 0.52 ppm from the respective dose groups In c omposited muscle, the maximum c ombined residues were <0.06 ppm from the 1.75 and 7 ppm dose groups, <0.07 ppm from the 21 ppm dose group, and 0.15 ppm from the 70 ppm dose group. Combined residues in muscle averaged 0.03, 0.03, 0.06, and 0.12 ppm from the 1.75, 7, 21, and 70 ppm dose groups, respectively. Following a 28 - day

recovery p eriod for hens dosed at 70 ppm, residues of each analy te were nondetectable «0 .003 ppm) in skin, liver, and muscle. Residues of each analy te were also <0.003 ppm in fat with the exception of IN- JT333, which had detectable residues (0.004 - 0.009 ppm) below the method LOQ. following the cessation of dosing average combined residues in eggs declined from 0.65 ppm at 2 days post- dose to 0.07 ppm by 9days post- dose. By

1 2 days postdose, residues of each analy

te, except IN- JT333, were <0.003 ppm in eggs, and residues of IN- JT333 declined to <0.003 ppm by

23 days post- dose. Cattle. For the cow study, the cattle were fed at 10 ppm/day f or 5 - days; approximately

2 0% of the total administered dose was excreted in urine and 53 - 60% was excreted in feces in 5 - days. Fourtenths to 1.2% of the total dose in urine was parent indicating extensive metabolism; parent represented 46 - 68% of the fecal activity. Thus, most residues were not absorbed; those residues that were absor

bed were extensively

metabolized. Less than 1% of the total administered dose was in6

milk, most of which was parent compound. The insecticidally active metabolite IN- JT333 was not found in milk. Residues in muscle represented less than 0.01% of the total administered dose most of which was parent. IN - JT333 was not detected in muscle. No other metabolites were seen above 10% of the dose, thus only parent and I

N- JT333 were monitored in the cattle feeding study. Cattle feeding study. A cattle feeding study was conducted with indoxacarb at doses of 7.5 ppm, 22.5 and 75 ppm. The mean KN128/KN127 concentrations were proportional to the dosing level in whole milk, skim milk, cream, muscle, fat, liver and kidney. Based on final residue values for the respective c ommodities contributing to the cattle diet, the anticipated dietary burden in dairy

c attle is 51.7 ppm and the anticipated dietary burden in beef cattle is 49.1 ppm. The proposed grape use will not increase the animal dietary burden. Based on standard curves constructed from data in the cattle feeding study, KN128/KN127 concentrations at the 51.7 -ppm feeding level are 0.123 ppm for whole milk, 0.033 ppm for skim milk and 1.46 ppm for cream. The KN128/KN127 concentrations at the 49.1 ppm feeding level are 0. 046 ppm for muscle, 1.37 ppm for fat, 0.012 ppm for liver and 0.026 ppm for kidney. Tolerances have been established at 1.5 ppm in fat (cattle, goat, horse, sheep and hog), 0.05 ppm in meat, 0.03 ppm in meat by-products, 0.15 ppm in milk and 4.0 ppm in mi lk fat. 7. Metabolite toxicology . In rats, indoxacarb was readily a bsorbed at low dose (5 mg/kg), but saturated at the high dose (150 mg/kg). I ndoxacarb was metabolized extensively, based on very l ow excretion of parent compound in bile and extensive excretion of metabolized dose in the urine and feces. Some parent compound remained unabsorbed and was excreted in the feces. No parent compound was excreted in the urine. The retention and elimination of the metabolite IN- JT333 from fat appeared to be the overall rate determining process for elimination of radioactive residues from the body. Metabolites in urine were cleaved products (containing only one radiolabel), while the major metabolites in the feces retained both radiolabels. Major metabolic reactions included hy

droxy lation of the indanone ring, hy drolysis of the carboxy

lmethy l group from the amino nitrogen and the opening of the oxadiazine ring, which gave rise to cleaved products. Metabolites were identified by mass spectral analysis, NMR, UV and/or by comparison to standards chemically

sy nthesized or produced by

microsomal enzy

mes. 8. Endocrine disruption . Li fespan, and multigenerational bioassays in mammals and acute and subchronic studies on aquatic organisms and wildlife did not reveal endocrine effects. Any endocrine related effects would have been detected in this definitive array o f required tests. The probability

of any such effect due to agricultural uses of indoxacarb is negligible. C. Aggregate Exposure Tolerances for indoxacarb are proposed to support agricultural use on succulent beans, dried beans, and the crops of subgroups 13 - 07 F and 13 - 07 H.

1. Dietary exposure . The chronic RfD of 0.02 mg/kg bw/day i s based on a NOAEL of7

2.0 mg/kg bw/day

from the subchronic rat feeding study, the subchronic rat neurotoxicity study, and the chronic/carcinogenicity study, using an uncertainty f actor of 100. The acute RfD for the general population is 0.12 mg/kg/day, based on the NOAEL of 12.5 mg/kg in the acute neurotoxicity study and an uncertainty

f actor of 100. The acute RfD for females 13 - 50 ye ars of age is 0.02 mg/kg/day, based on the NOAEL

of 2 mg/kg/day

observed in the developmental rat toxicity study and using an uncertainty

factor of 100. i. Food. Chronic dietary

exposure assessment. Chronic dietary exposure resulting from the currently

a pproved use of indoxacarb on apples, Crop group 5 (brassica vegetables), cotton, pears, peppers, sweet corn, tomatoes, eggplant, alfalfa, head and leaf lettuce, peanuts, potatoes, soy beans, cranberries (current Section 18 use) and the proposed uses on grapes, leafy B rassica, leafy greens crop subgroup 4A (except spinach), spinach, leaf petioles crop subgroup 4B, tuberous and corm vegetables crop subgroup 1C, pome fruits crop group 11 (except pear), okra, pea (Southern) and mint are well within acceptable limits for all sectors of the population. The Chronic Module of the Dietary

Exposure Evaluation Model (DEEM, Exponent, Inc., formerly Novigen Sciences, Inc., Version 7.87) was used to conduct the assessment with the reference dose (RfD) of 0.02 mg/kg/ day. The analysis used overall mean field trial values, processing factors and projected peak percent crop treated values. Secondary residues in milk, meat and poultry products were also included in the analysis. The chronic dietary exposure to indoxacarb is 0.000185 mg/kg/day, and utilizes 1% of the Rf

D for the overall U.S. population. The exposure of the most highly exposed subgroup in the population, children age 1 - 2 ye ars, is 0.000347 mg/kg/day, and utilizes 2% of the RfD. The table below lists the results of this analysis, which indicate large margins of safety f or each population subgroup and very l ow probability

o f effects resulting from chronic exposure to indoxacarb.8

Subgroup Maximum Dietary Exposure (mg/kg/day

) % RfD U.S Population All infants Males 13 - 19 M ales 20+ Seniors 55+ Children 1 - 2 Children 3 - 5 Children 6 - 12 Youth 13 - 19 Adults 20 -49 Adults 50+ Females 13 - 19 (not preg or nursing) Females 20+ (not preg or nursing) 0.000185 0.000126 0.000183 0.000165 0.000186 0.000347 0.000315 0.000191 0.000171 0.0001 63 0.000186 0.000157 0.000179 1 1 1 1 1 2 2 1 1 1 1 1 1 Acute dietary

exposure. Acute dietary

exposure resulting from the proposed uses and the currently

a pproved use of indoxacarb on apples, Crop Group 5 (brassica vegetables), cotton, pears, peppers, sweet corn, tomatoes, eggplant, alfalfa, head and leaf lettuce, peanuts, soy beans, potatoes, cranberries (current Section 18 use) and the proposed uses on grapes, leafy B rassica, leafy greens crop subgroup 4A (except spinach), spinach, leaf petioles crop subgroup 4B, tuberous and corm vegetables crop subgroup 1C, pome fruits crop group 11 (except pear), okra, pea (Southern) and mint are well within acceptable limits for all sectors of the population. The Dietary Exposure Evaluation Model (DEEM, Exponent, Inc., formerly N ovigen Sciences, Inc., Version 7.87) was used to conduct the assessment. M argins of exposure (MOE) were calculated based on a NOAEL of 12 mg/kg/day f or children and the general population (Pesticide Fact Sheet for Indoxacarb). An endpo int of concern attributable to a single dose was not identified for women of childbearing age; therefore an acute RfD was not established for this population. The Tier 3 analysis used distributions of field trial residue data adjusted for projected peak p ercent crop treated. Secondary

residues in milk, meat and poultry products were also included in the analysis. The results of this analysis are given in the table below. The percent of the acute population adjusted dose (a PAD) for all population subgrou ps shows that an adequate margin of safety exists in each case. Thus, the acute dietary s afety o f indoxacarb for established and the follow - on use clearly

m eets the FQPA standard of reasonable certainty o f no harm and presents acceptable acute dietary

risk .9

Subgroup 99.9th Percentile Of Exposure Exposure (mg/kg/day

) % Acute

population adjusted dose (aPAD) U.S. Population All infants Males 13 - 19 Males 20+ Seniors 55+ Children 1 - 2 Children 3 - 5 Children 6 - 12 Youth 13 - 19 Adults 20 - 49 Adults 50+ 0.02026 7 0.018458 0.029223 0.019257 0.020072 0.036020 0.005358 0.017498 0.022245 0.018887 0.019883 17

15 24 16 17 23 30 15 19 16 17 ii. Drinking water . Indoxacarb is highly u nlikely to contaminate groundwater resources due to its immobility

in soil, low water solubility, high soil sorption, and moderate soil half - life. Based on the PRZM/EXAMS and SCI- GROW models the estimated environmental concentrations (EECs) of indoxacarb and its R- enantiomer for acute exposures are estimated to be 6.84 parts per billion (ppb) for surface water and 0.0025 ppb for ground water. The EECs for chronic exposures are estimated to be 0.316 ppb for surface water and 0.0025 ppb for ground water. Drinking water levels of comparison (DWLOCs), theoretical upper allowable limits on the pesticide = s concentration in drinking water, were calculated to be much higher than the EECs. The chronic DWLOCs ranged from 198 to 697 ppb. The acute DWLOCs ranged from 440 to 3890 ppb. Thus, exposure via drinking water is accepta ble. 2. Non -dietary exposure . Indoxacarb product registrations for residential non- food uses have been approved. Non- occupational, non- dietary exposure for DPX- MP062 has been estimated to be extremely

small. Therefore, the potential for non- dietary exposure is insignificant. D. Cumulative Effects

EPA's consideration of a common mechanism of toxicity i s not necessary

a t this time because there is no indication that toxic effects of indox acarb would be cumulative with those of any other chemical compounds. Oxadiazine chemistry i s new, and indoxacarb has a novel mode of action compared to currently registered active ingredients.10

E. Safety Determination

1. U.S. population . Dietary a nd occupational exposure will be the major routes of exposure to the U.S. population, and ample margins of safety have been demonstrated for both situations. The chronic dietary exposure to indoxacarb is 0.00018 5 mg/kg/day, which utilizes 1% of the RfD for the overall U.S. population, using mean field trial values, processing factors and projected peak percent crop treated values. The percent of the acute population adjusted dose (17% aPAD) for the overall U.S. p opulation shows that an adequate margin of safety exists. U sing only PHED data levels A and B (those with a high level of confidence), MOEs for occupational exposure are 650 for mixer/loaders and 1351 for airblast applicators (worst- case). B ased on the c ompleteness and reliability of the toxicity

data and the conservative exposure assessments, there is a reasonable certainty

t hat no harm will result from the aggregate exposure of residues of indoxacarb including all anticipated dietary exposure and all ot

her non- occupational exposures. 2. Infants and children . Chronic dietary exposure of the most highly exposed subgroup in the population, children age 1 - 2 ye ars, is 0.000347 mg/kg/day or 2% of the RfD. For all infants, t he exposure accounts for 1% of the RfD. F or acute exposure at the 99.9th percentile (based on a Tier 3 assessment) the exposure was 0.005358 mg/kg/day ( 30% aPAD) for children 3 - 5 and 0.018458 mg/kg/day

( 15% aPAD) for all infants. Residential uses of indox acarb have been approved and exposure is calculated to be extremely minimal. The estimated levels of indoxacarb in drinking water are well below the below the DWLOC. Based on the completeness and reliability of the toxicity

data, the lack of toxicological endpoints of special concern, the lack of any indication that children are more sensitive than adults to indoxacarb, and the conservative exposure assessment, there is a reasonable certainty t hat no harm will result to infants and children from the aggregate exposure of residues of indoxacarb, including all anticipated dietary exposure and all other non- occupational exposures. Accordingly, there is no need to apply an additional safety

factor for infants and children. F. International Toler

ances To date, numerous tolerances exist for indoxacarb residues in various food and feed crops and foods of animal origin in at least 25 countries.