**EPA REGISTRATION DIVISION -**  **COMPANY NOTICE OF FILING OF**

**PESTICIDE PETITION EPA Registration Division contact: Sidney Jackson (703) 305**  **- 7610**  **Interregional Research Project Number 4 Pesticide Petition Number: 3E8204**  EPA has received a pesticide p etition ( 3E8204 ) from Interregional Research Project #4 , Interregional Research Project #4 (IR - 4), Rutgers, The State University of New Jersey , 500 College Road East, Suite 201 W, Princeton, NJ 08540 request ing, pursuant to section 408(d) of the Federal Fo od, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing or revising the tolerance s for residues of the insecticide spinosad, including its metabolites and degradates. Compliance with the tolerance levels is to be determined by measuring only the two related active ingredients: **Spinosyn A** (Factor A: CAS # 131929

– 60

– 7) or 2 - [(6 - deox y2,3,4 - tri - O - methyl - α - L - manno - py ranosyl)oxy] - 13 - [[5 - (dimethylamino) - tetrah ydro - 6 - methyl - 2H - py

ran - 2 - yl ]oxy] - 9 - eth yl - 2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b tetradecah ydro - 14 - methyl - 1H - as - Indaceno[3,2 - d]oxacyclododecin - 7,15 - dione; and **Spinosyn D** (Factor D; CAS # 13192 9

– 63

–0) or 2 - [(6 - deox y- 2,3,4 - tri - O - methyl - α - L - manno - py

ranos yl )ox y] - 13 - [[5 - (dimethyl - amino) - tetrahydro - 6 - methyl - 2H - py ran - 2 - yl ]oxy] - 9 - eth yl - 2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b - tetradecahydro - 4,14 - methyl - 1H as - Indaceno[3,2 - d]oxacyclododecin - 7,15 - dione ] in or on the raw agricultural commodity c offee, green bean at 0 .2 parts per million (ppm) , coffee, instant at 0.4 ppm, coffee, roasted bean at 0.4 ppm, cottonseed subgroup 20C at 0.02 ppm, caneberry subgroup 13.07A at 0.7 ppm, bushberry subgroup 13 - 07B, except lingonberry at 0.2 5 ppm, fruit, small, vine climbing, except fuzzy kiwifruit subgroup 13 - 07F at 0.5 ppm, b erry, low growing, subgroup 13 - 07G, except blueberry , lowbush, and cranberry at 1.0 ppm, fruit, pome group 11 - 10 at 0.2 ppm, vegetable, fruitin g, group 8 - 10 at 0.4 ppm, fruit, citrus, group 10 - 10 at 0.3 ppm, fruit, stone, group 12 - 12 at 0.2 ppm, o nion, bulb, subgroup 3 - 07A at 0.1 ppm, onion, green, subgroup 3 - 07B at 2.0 ppm, nuts, tree, group 14 - 12 at 0.1 ppm , Quinoa, grain at 1.0 ppm . EPA has d etermined 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. The Agency

has concluded that spinosad is considered toxicologicall y identical to another pesticide, spinetoram. This conclusion is based on the following: (1) Spinetoram and spinos ad are large molecules with nearl y identical structures; and (2) the toxicological profiles for each are similar (generalized sy stemic toxicity) with similar doses and endpoints chosen for human - health risk assessment. Spinosad and spinetoram should be con sidered toxicologically identical in the same manner that metabolites are generall y considered toxicologically identical to the parent. A. Residue Chemistry2

1. Plant metabolism. Per the Federal Register: April 15, 1998 (Vol 63, No 72) OPP - 300644; FRL - 57 85 - 7, the nature of the residue of spinosad in plants has been studied in several plants (apple, cabbage, cotton, tomato and turnip) and is adequatel y understood. EPA determined the rotational crop study showed no carryover of measurable spinosad related residues in representative test crops (lettuce, radish, and wheat). Tolerances for enforcement are established for spinosad based on the residue definition of Spinosy

n A (Factor A) plus Spinosy n D (Factor D). 2. Analytical method. EPA has determined that adequate anal yt ical methods are available for enforcement purposes for spinosad residues in plant and animal matrices. Enforcement methods are available for spinosad residues in a variety of plant matrices including; a number of high - performance liquid chromatograph y (HPL C)/ultraviolet (UV), and HPL C/MS (mass spectrometry) methods as well as various immunochemical methods. For more details on relevant enforcement methods, see EPA Memorandum

– “SUBJECT: Spinosad and Spinetoram; Human - Health Assessment Sco ping Document in Support of Registration Review” dated August 9, 2011. 3. Magnitude of residues. The IR - 4 spinosad MOR trials in coffee support tolerances of 0.2 ppm for coffee, green bean and 0.4 ppm for coffee, ins tant and coffee, roasted bean . Residues of spinosad were determined following three foliar applications at five field locations in Hawaii and Puerto Rico during the 1999 and 200 8 growing seasons. Spinosad was applied at a target rate of 0.156 lb ai/A, fo r a total of approximately

0.468 lb ai/A. Applications were made 4 to 7 day s apart and timed so that green coffee beans were collected 7 d ay s after the final application . Additionally , in each trial, one site was treated with 0.7 lb ai/A per application f or a total of 2.1 lb ai/A per season; in 2008, green coffee beans from this exaggerated application rate were processed to roasted beans and freeze - dried coffee. In the 1999 trials, s pinosad residues were determined b y the Department of Environmental Bioc hemistry at the University

of Hawaii, Honolulu, HI using a procedure based on Dow AgroSciences methods GRM 96.11 and GRM 96.11.S1. Inthe 2008 trials, spinosad residues were determined by the Department of Molecular Biosciences & Bioengineering at the Uni versity of Hawaii, Honolulu, HIusing a procedure based on Dow AgroSciences method GRM 00.6.S3. The lowest level of method validation (LLMV) was 0. 01 ppm in green coffee beans in the 1999 trial and 0.1 ppm in the 2008 trial, and 0.018 ppm in roasted beans and freeze dried coffee in the 1999 trial and 0.2 ppm in the 2008 trial . All spinos ad residues were below the LLMV for the green coffee beans treated at the target application rate of 0.156 lb ai/A and for the processed coffee commodities . In the 1999 trials at the exaggerated rate, residues in green coffee beans ranged from 0.061 to 0.065 ppm . IR - 4 reques ts revisions to the following crop groups/subgroups based upon established tolerances: onion, bulb subgroup 3 - 07A; onion, green subgroup 3 - 07B; fruiti ng vegetable group 8 - 10; citrus fruit group 10 - 10; pome fruit group 11 - 10; stone fruit group 12 - 12; caneberry subgroup 13 - 07A; bushberry subgroup 13 - 07B , except lingonberry ; small fruit vine, climbing subgroup, except fuzzy kiwifruit 13 - 07F; low growing be rry subgroup 13 - 07G, except blueberry , lowbush, and cranberry ; tree nut group 14 - 12; and cottonseed subgroup 20C .3

B. Toxicological Profile . Per the Federal Register: April 15, 1998 (Vol 63, No 72) OPP 300644; FRL - 5785 - 7, EPA determined the toxicological profile and endpoints for spinosad are adequate for risk assessment evaluations and determination of FQPA. For recent spinosad decisions, per Federal Register: December 5, 2007 (Volume 72, Number 233); FRL - 8339 - 8, EPA employed slightly revised endpoints based on their decision that spinetoram is toxicologically identical to spinosad. EPA select ed the lowest of the spinosad and spinetoram endpoints for each exposure scenario. A summary of the toxicological endpoints for spinosad and spinetoram used for human risk assessment can be found at http://www.regulations.gov in docket EPA - HQ - OPP - 2007 - 0310. Relevant information is summarized in the subsections below. Under the new 40 CFR Part 158 data requirements for sp inosad/spinetoram, there are no missing studies at this time. There was no evidence of increased pre - and post - natal susceptibility based on prenatal developmental toxicity

studies (rat and rabbit) and 2 - generation reproductive toxicity studies (rat) with either spinosad or spinetoram. In addition, there was no evidence of neurotoxicity

in the toxicity

database that included acute and subchronic neurotoxicity studies with spinosad and an acute neurotoxicity study with spinetoram. An immunotoxicity

study has been conducted with Spinosad and EPA’s initial review indicate the level of concern for immunotoxicity is low ( EPA, DP# 446932, August 9, 2011 ). 1. Acute toxicity. No appropriate endpoint attributable to a single dose was identified; the EPA has not es tablished an acute reference dose ( RfD ) for spinosad or spinetoram. 2. Genotoxic i ty. Assay s for genotoxicity consisting of a bacterial reverse mutation assay (Ames test), and in vitro assay for cy togenetic damage using the Chinese hamster ovary cells, an in vitro mammalian gene mutation assay using l ymphoma cells, an in vitro assay for DNA damage and repair in rat hepatocy tes, and an in vivo cy

togenetic assay

in the mouse bone marrow (micronucleus test) have been conducted with spinosad. These studies sh ow a lack of genotoxicity . 3. Reproductive and developmental toxicity. Spinosad caused decreased body weights in maternal rats given 200 mg/kg/day by gavage in a developmental study (highest dose tested). This was not accompanied by embryotoxicity , fetal toxicity , or teratogenicity. The no - observed - adverse - effect levels (NO A ELs) for maternal and fetal toxicity in rats were 50 and 200 mg/kg/day , respectively . A developmental study in rabbits showed that spinosad caused decreased body weight gain and two abortions attributed to inanition in maternal rabbits at 50 mg/kg/day (highest dose tested). Maternal toxicity was not accompanied by either embryo toxicity , fetal toxicity , or teratogenicity. The NOELs for maternal and developmental effects in rabbits were 10 and 50 mg/kg/day , respectivel y. In a two - generation reproduction study in rats, parental toxicity

was observed in both males and females given 100 mg/kg/day (highest dose tested). Effects in the offspring (decreased litter size and pup weight) at 100 mg/kg/day were attributed to maternal toxicity . The sy stemic and reproductive NO A ELs were both 10 mg/kg/day . EPA has determined that reliable data show that it would be safe for infants and children to reduce the 10X FQPA safety factor to 1X.4 4. S ubchronic toxicity. Both Short - term endpoints (inhalation and incidental oral) were established based on the Oral NOAEL of 4.9 mg/kg/day from the subchronic feeding study in dogs with spinosad and a LOC for MOEs of 100. 5. Chronic toxicity. EPA used the lowest NOAEL of 0.249 mg/kg/day from the chronic toxicity

study in dogs for spinetoram and a 100X UF to establish a chronic reference dose ( cRfD ) of 0.0249 mg/kg/day for both spinosad and spinetoram. Spinosad is considered ``Not likely to be Carcinogenic to Humans''. 6. Animal metabolism. The nature of spinosad residue in animals is understood based on livestock studies in ruminants (oral and dermal) and poultry (oral) (DP # 316077, August 2, 2006). ADME studies in rats indicate spinosad is rapidl y abso rbed and extensively

metabolized. Also the rat metabolism studies showed no major differences between the bioavailability , routes or rates of excretion, or metabolism of Factor A or Factor D. Urine and fecal excretions were almost completed in 48 - hours p ost - dosing. In addition, the routes and rates of excretion were not affected by repeated administration. EPA recently indicated that for fish/shellfish within the risk assessment estimates of the total residue within edible tissues is applicable (EPA, DP # 316077, August 2, 2006). Total edible residues in fish have been extensively characterized within BCF studies (MRID 43557601, 44557734, 47355801 ) . 7. Metabolite toxicology . Results of the plant and animal metabolism studies and toxicity testing have been assessed. Per Federal Register: April 15, 1998 (Vol 63, No 72) FRL - 5785 - 7, EPA concluded that the spinosad metabolites/fermentation impurities (Factor B, Factor B of D, Factor K, and other related Factors) were no t of greater toxicological concern than the two parent compounds. Metabolite toxicity has been addressed b y establishment of the residue for tolerance purposes as the parent materials. In addition, for risk assessment purposes, the total residue in water and edible fish is now conservativ el y considered. 8. Endocrine disruption . There is no evidence to suggest that spinosad has an effect on an y endocrine system. C. Aggregate Exposure 1. Dietary exposure. i. Acute exposure. No quantitative acute dietary exposure assessment has been requ ired for spinosad. ii. Chronic exposure. Spinosad and spinetoram are deemed toxicologicall y equivalent b y EPA. Based on the similarity of the insecticides and the anticipated markets for each, it is unlikely

that spinosad and spinetoram will be applied t o the same crop. Hence, EPA aggregated exposure b y either assuming that all commodities contain spinosad (because side - by- side spinosad and spinetoram residue data indicated that spinetoram residues were less than or equal to spinosad residues) or summing the percentage of a crop that would be treated with spinosad and the percentage that would be treated with spinetoram. i. Food. The chronic dietary exposure assessment (EPA, DP# 380915 , August 18,5

2010 ) was recreated in Dietary Exposure Evaluation Model - Food Consumption Intake Database (DEEM - FCID) (version 3.14 ) as a starting point **.** The new proposed tolerance values for coffee commodities were included in this dietary assessment. The EPA anal ys is assumed 100% crop treated for man y commodities, toleran ce - level residues, and default processing factors, but with several exceptions: average field trial residues were applied for the cucurbit vegetables (group 9), citrus (group 10), pome fruit (group 11), cereal grain (group 15), herbs (group 19a), spices ex cept black pepper (group 19b), banana and plantain, strawberry , and grape; average USDA Pesticide Data Program (PDP) detected residues were applied for cherry and peach, with the peach residues applied to fennel as well; experimental processing factors were applied for corn meal, corn oil, corn flour, corn starch, wheat flour, wheat germ, apple juice, raisin, and orange juice, with the orange juice processing factor applied to all citrus juice. Ruminant and hog residues were estimated based on reasonabl y b alanced dietary burdens and extrapolation from a dermal pour - on study (a cancelled use) to the registered premise application for estimation of residues resulting from dermal absorption. Poultry residues were also estimated based on reasonabl y balanced di etary burdens and the premise application. ii. Drinking water. Drinking water estimates were previously determined based on EPA screening models and concentrations were directly entered into the dietary exposure model. For spin osad , estimated environment al concentrations (EECs) for chronic exposures are conservatively calculated based on a total residue approach to be 10.5 ppb for surface water using the First Index Reservoir Screening Tool (FIRST) and 1.1 ppb for ground water using the Screening Concentration in Ground Water (SCI - GROW) model (EPA, DP#331271, July

28, 2006) . Thus, for the joint chronic dietary risk assessment, EPA has used the water concentration value of 10.5 ppb to assess the contribution to drinking water. This value was supported b y a 2010 drinking water assessment in support of a seed treatment use for spinosad (EPA, DP#377550, November 15, 2010). 2. Non - dietary exposure . EPA has determined there is potential for residential handler and post - application exposures to spinosad/spinet oram. Because spinosad and spinetoram control similar pests, EPA concluded these products will not be used in combination with each other and combining the residential exposures is unnecessary . The most recent residential exposure assessment was performe d in 2011 ( EPA, DP# 446932, August 9, 2011 ), however in 2012, new “Standard Operating Procedures (SOPs) for Residential Pesticide Exposure Assessment” were released by EPA . Residential exposure assessments have been updated to reflect the new SOPs. S hort - term residential inhalation risks were estimated for adult residential handlers, as well as short - term post application incidental oral risks for toddlers, based on applications to home lawns, home gardens and ornamentals. Additionally , short - term and intermediate - term post application incidental oral risks for toddlers were estimated based on a cat/kitten spot - on application. D. Cumulative Effects EPA has not made a common mechanism of toxicity finding as to spinosad and6

any other substances and spinos ad does not appear to produce a toxic metabolite produced b y other substances. HED’s Hazard Assessment and Policy Committee noted that toxicologically

equivalent does not imply a cumulative assessment which involves the concepts of mechanism of toxicity and potency . For the purposes of tolerance action, it is not assumed that the spinosy ns have a common mechanism of toxicity with other substances. E. Safety Determination The proposed actions of this petition have been added via DEEM to EPA’s most recent dietary assessment for spinetoram/spinosad (EPA, DP#380915, August 18, 2010) and the residential assessment has been updated to reflect current EPA practices. The additional exposure from the proposed coffee use is estimated to be 0 to 0.02% of the cPAD. Short - term, intermediate - term, and chronic aggregate exposure estimates all resulted in MOEs that were above the establishe d Level of Concern (LOC) of 100 . Dow AgroSciences concludes with reasonable certainty that no harm will result to the general popul ation or infants and children from the aggregate exposure to spinetoram residues from these uses. 1. U.S. population. The resulting dietary (food and drinking water) exposure estimates are not of concern to HED; exposure for the general population is estimated as <11% of the cPAD. When the dietary exposure is summed with the estimated residential inhalation exposure, the resulting short - term aggregate MOE value was approximately 1800. 2. Infants and children . EPA has determined that reliable data allow a reduction of the FQPA safety factor to 1X for infants and children **.** The resulting dietary exposure for the most exposed subpopulation (children 1 to 2 years) is estimated as <28% of the cPAD. Short - term post - application risks were estimated for toddle rs, based on application to home lawn s , home gardens, ornamentals , and pets and risks were not of concern given that resulting MOEs were > 500 . The resulting short - term aggregate MOE values were > 30 0 and are, therefore, not of concern to HED. Intermediate - term post application risks were estimated for toddlers, based on application to pets and risks were not of concern given resulting MOEs were ≥700. The resulting intermediate - term aggregate MOE values were >200 and are, therefore, not of concern to HED. F. International Tolerances A variety of international and CODEX MRL s are in place for spinosad. The USDA MRLdatabase, the third party dat abase Homologa, the EU SANCO website, the Australian MRLwebsite, and the Japan MRLwebsite were queried for MRLs germane to this petition. These MRLs are listed to the best of our knowledge; no claim is made regarding the verification of these values rel ative to the national authorities. **Spinosad Comm**  **odity Existing MRL**  **a (ppm)**  **Regulatory Authority** Coffee beans 0.02 EU, Iceland, Norway, Switzerland Coffee beans *0.01 Australia Coffee 0.2 Brazil7

athe * and T notations are direct translations from the c ountry website listings.