Flonicamid; Pesticide Tolerance, 51604-51615 [05-17128]

Download as PDF 51604 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations Dated: August 19, 2005. Lois Rossi, Director, Registration Division, Office of Pesticide Programs. 1. The authority citation for part 180 continues to read as follows: I Authority: 21 U.S.C. 321(q), 346a and 371. Therefore, 40 CFR chapter I is amended as follows: I 2. In § 180.554, the table in paragraph (b) is amended by alphabetically adding commodities to read as follows: I PART 180—[AMENDED] § 180.544 Methoxyfenozide; tolerance for residues. * Commodity * * (b) * * * Parts per million sorghum, grain sorghum, grain, forage sorghum, grain, stover * * * * * BILLING CODE 6560–50–S ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 180 [OPP–2005–0217; FRL–7731–6] Flonicamid; Pesticide Tolerance Environmental Protection Agency (EPA). ACTION: Final rule. AGENCY: SUPPLEMENTARY INFORMATION: I. General Information SUMMARY: This regulation establishes a tolerance for combined residues of flonicamid and its metabolites in or on certain plant and livestock commodities. ISK Biosciences requested this tolerance under the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality Protection Act of 1996 (FQPA). DATES: This regulation is effective August 31, 2005. Objections and requests for hearings must be received on or before October 31, 2005. ADDRESSES: To submit a written objection or hearing request follow the detailed instructions as provided in Unit VI. of the SUPPLEMENTARY INFORMATION. EPA has established a docket for this action under Docket identification (ID) number OPP–2005– 0217. All documents in the docket are listed in the EDOCKET index athttp:// www.epa.gov/edocket. Although listed in the index, some information is not publicly available, i.e., CBI or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the Internet and will be publicly available only in hard copy form. Publicly available docket materials are available either electronically in EDOCKET or in hard copy at the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1801 S. Bell St., 16:14 Aug 30, 2005 Jkt 205001 Arlington, VA. This docket facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The docket telephone number is (703) 305–5805. FOR FURTHER INFORMATION CONTACT: Ann Sibold, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001; telephone number: (703) 305–6502; e-mail address:sibold.ann@epa.gov. A. Does This Action Apply to Me? You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially affected entities may include, but are not limited to: • Crop production (NAICS 111), e.g., agricultural workers; greenhouse, nursery, and floriculture workers; farmers. • Animal production (NAICS 112), e.g., cattle ranchers and farmers, dairy cattle farmers, livestock farmers. • Food manufacturing (NAICS 311), e.g., agricultural workers; farmers; greenhouse, nursery, and floriculture workers; ranchers; pesticide applicators. • Pesticide manufacturing (NAICS 32532), e.g., agricultural workers; commercial applicators; farmers; greenhouse, nursery, and floriculture workers; residential users. This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in this unit could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. If you have any questions regarding the applicability of this action to a particular entity, consult PO 00000 Frm 00046 Fmt 4700 Sfmt 4700 * Expiration/revocation date 0.05 15 125 [FR Doc. 05–17131 Filed 8–30–05; 8:45 am] VerDate Aug<18>2005 * 12/31/2007 12/31/2007 12/31/2007 the person listed underFOR FURTHER INFORMATION CONTACT. B. How Can I Access Electronic Copies of this Document and Other Related Information? In addition to using EDOCKET (http:// www.epa.gov/edocket/), you may access this Federal Register document electronically through the EPA Internet under the ‘‘Federal Register’’ listings at http://www.epa.gov/fedrgstr/. A frequently updated electronic version of 40 CFR part 180 is available at E-CFR Beta Site Two at http:// www.gpoaccess.gov/ecfr/. To access the OPPTS Harmonized Guidelines referenced in this document, go directly to the guidelines athttp://www.epa.gpo/ opptsfrs/home/guidelin.htm/. II. Background and Statutory Findings In the Federal Register of May 23, 2003 (68 FR 28218) (FRL–7307–5), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 3F6552) by ISK Biosciences, 7470 Auburn Road, suite A, Concord, Ohio 44077. The petition requested that 40 CFR part 180 be amended by establishing a tolerance for the combined residues of the insecticide flonicamid, [N-(cyanomethyl)-4trifluoromethylnicotinamide] and its metabolites, TFNA, (4trifluoromethylnicotinic acid), TFNAAM, (4-trifluoromethylnicotinamide) and TFNG, [N-(4trifluoromethylnicotinoyl)glycine] in or on the raw agricultural commodities: Celery, at 1.2 parts per million (ppm); cotton, at 0.5 ppm; cotton, gin trash, at 6.0 ppm; cotton, hulls, at 1.0 ppm; cotton, meal, at 1.0 ppm; fruit, pome, group 11, at 0.2 ppm; fruit, stone, group 12, except plum and fresh prune plum, at 0.7 ppm; lettuce, head, at 1.0 ppm; lettuce, leaf, at 4.0 ppm; plum, at 0.1 ppm; potato, at 0.2 ppm; potato, flakes, at 0.4 ppm; prune, fresh, at 0.1; spinach, at 9.0 ppm; tomato, paste, at 2.0 ppm; tomato, puree, at 0.5 ppm; vegetable, E:\FR\FM\31AUR1.SGM 31AUR1 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations cucurbit, group 9, at 0.4 ppm; vegetable, fruiting, group 8, at 0.4 ppm; by establishing tolerances for the combined residues of the insecticide flonicamid, [N-(cyanomethyl)-4trifluoromethylnicotinamide] and its metabolite TFNA-AM, (4trifluoromethylnicotinamide) in animal tissues and poultry meat byproducts:Cattle, fat, at 0.01 ppm; cattle, meat, at 0.04 ppm; eggs, at 0.02 ppm; goat, fat, at 0.01 ppm; goat, meat, at 0.04 ppm; hog, fat, at 0.01; hog, meat, at 0.01 ppm; horse, fat, at 0.01 ppm; horse, meat, at 0.04 ppm; milk, at 0.02 ppm; poultry, fat, at 0.01 ppm; poultry, meat, at 0.01 ppm; poultry, meat byproducts, at 0.01 ppm; sheep, fat, at 0.01 ppm; sheep, meat, at 0.04 ppm; by establishing tolerances for the combined residues of the insecticide flonicamid [N-(cyanomethyl)-4trifluoromethylnicotinamide] and its metabolites TFNA, (4trifluoromethylnicotinic acid) and TFNA-AM, (4trifluoromethylnicotinamide) in the animal meat byproducts: cattle, meat byproducts, at 0.06 ppm; goat, meat byproducts, at 0.06 ppm; hog, meat byproducts, at 0.01 ppm; horse, meat byproducts, at 0.06 ppm; and sheep, meat byproducts, at 0.06 ppm. That notice included a summary of the petition prepared by ISK Biosciences, the registrant. One comment was received on the notice of filing. EPA’s response to this comment is discussed in Unit IV.C. Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is ‘‘safe.’’ Section 408(b)(2)(A)(ii) of FFDCA defines ‘‘safe’’ to mean that ‘‘there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.’’ This includes VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 exposure through drinking water and in residential settings, but does not include occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to ‘‘ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue. . . .’’ EPA performs a number of analyses to determine the risks from aggregate exposure to pesticide residues. For further discussion of the regulatory requirements of section 408 of FFDCA and a complete description of the risk assessment process, see the final rule on Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997, FRL–5754– 7) III. Aggregate Risk Assessment and Determination of Safety Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure, consistent with section 408(b)(2) of FFDCA, for a tolerance for combined residues of flonicamid and its metabolites on various crop and livestock commodities at levels set forth in the list below. Tolerances for combined residues of flonicamid and its metabolites in/on crops and livestock commodities. 1. Recommended tolerances for combined residues of flonicamid and its metabolites TFNA, TFNG and TFNAAM in/on crops. Cotton, undelinted seed at 0.50 ppm Cotton, gin byproducts at 6.0 ppm Cotton, hulls at 2.0 ppm Cotton, meal at 1.0 ppm Fruit, pome, group 11 at 0.20 ppm Fruit, stone, group at 12 0.60 ppm Potato 0.20 at ppm Potato, granular/flakes at 0.40 ppm PO 00000 Frm 00047 Fmt 4700 Sfmt 4700 51605 Spinach at 9.0 ppm Tomato, paste at 2.0 ppm Tomato, puree at 0.50 ppm Vegetable, cucurbit, group at 0.40 ppm Vegetable, fruiting, group at 0.40 ppm Vegetable, leafy except Brassica group 4, except spinach at 4.0 ppm 2. Recommended tolerances for combined residues of flonicamid and its metabolites TFNA and TFNA-AM in/on livestock commodities. Cattle, fat at 0.02 ppm Cattle, meat at 0.05 ppm Egg at 0.03 ppm Goat, fat at 0.02 ppm Goat, meat at 0.05 ppm Horse, fat at 0.02 ppm Horse, meat at 0.05 ppm Milk at 0.02 ppm Poultry, fat at 0.02 ppm Poultry, meat at 0.02 ppm Poultry, meat byproducts at 0.02 ppm Sheep, fat at 0.02 ppm Sheep, meat at 0.05 ppm Cattle, meat byproducts at 0.08 ppm Goat, meat byproducts at 0.08 ppm Horse, meat byproducts at 0.08 ppm Sheep, meat byproducts at 0.08 ppm EPA’s assessment of exposures and risks associated with establishing the tolerance follows. A. Toxicological Profile EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children. Specific information on the studies received and the nature of the toxic effects caused by flonicamid as well as the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL) from the toxicity studies are discussed in Table 1 of this unit. E:\FR\FM\31AUR1.SGM 31AUR1 51606 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations TABLE 1.—SUBCHRONIC, CHRONIC AND OTHER TOXICITY OF FLONICAMID Guideline No. Study Type Dose Levels Results 870.3100 90–Day oral toxicity rodents (rats) 28–day range-finding 0, 50 (males), 200, 1,000,2,000 (males), or 5,000(females) ppm (3.08, 12.11,60.0, or 119.4 mg/kg/day,males and 14.52, 72.3, or340.1 mg/kg/day, females) 0, 50 (males), 100, 500, 1,000,5,000 or 10,000 (females)ppm (3.61, 7.47, 36.45,73.8, or 353.4 mg/kg/day,males and 8.36, 41.24, 81.9,372.6, or 642 mg/kg/day,females) NOAEL is 200 ppm (12.11 mg/kg/day) formales and 1,000 ppm (72.3 mg/kg/day) forfemales LOAELs were 1,000 ppm (60.0 mg/kg/day) formales based on changes in the kidney (hyalinedeposition) and 5,000 ppm (340 mg/ kg/day) forfemales based on kidney (hyaline deposition)and liver changes (centrilobular hypertrophy) NOAEL is 100 ppm (7.47 mg/kg/day) for malesand 1,000 ppm (81.9 mg/kg/day) for females. LOAELs were 500 ppm (36.45 mg/kg/day) formales based on changes in the kidney (hyalinedeposition) and 5,000 ppm for females (372.6mg/kg/day) based on kidney (hyalinedeposition), liver changes (centrilobularhypertrophy), hematological effects (anemia)and clinical chemistry (increased cholesterol) 870.3100 90–Day oral toxicity rodents (mice) 0, 100, 1,000 or 7,000 ppm(0, 15.25, 153.9 or 1,069mg/kg bw/ day in males,and 0, 20.10, 191.5, or 1,248mg/kg bw/day in females) NOAEL is 100 ppm (males: 15.25 mg/kgbw/ day, females: 20.10 mg/kg bw/day) LOAEL is 1,000 ppm in (males: 153.9 mg/ kgbw/day; females: 191.5 mg/kg bw/day) basedon extramedullary hematopoiesis of the spleen Many of the tissues/organs recommended byGuideline 870.3100 were not histologicallyexamined in any dose group, but this study isnot required and serves as a range-findingstudy for the mouse carcinogenicity study.Therefore, it is classified as acceptable, non-guideline study 870.3150 90–Day oral toxicity (nonrodents- dogs) 0, 3, 8, 20, or 50 (females) mg/kg bw/day NOAEL is 8 mg/kg/day in males and 20 mg/kg/ day for female LOAEL is 20 mg/kg/day in males and 50 mg/ kg/day in females, based on acute clinical signs in males and females (vomiting, first observed on Day 1 and last observed on Day 90), clinical pathology at 7 weeks (increased total protein levels in males, lower red blood cells and higher reticulocytescounts in females), increased adrenal weights in males, decreased thymusgland weights in males, and increased kidney tubular vacuolation infemales at study termination 870.3200 28–Day dermal toxicity (rats) 0, 20, 150, or 1,000 mg/kg/day NOAEL is 1,000 mg/kg/day LOAEL is >1,000 mg/kg/day 870.3700 Prenatal developmental toxicity (rats) 0, 20, 100 or 500 mg/ kg bw/day Maternal NOAEL is 100 mg/kg bw/day LOAEL is 500 mg/kg bw/day, based onincreased liver weight, and liver and kidneypathological changes (hypertrophy ofcentrilobular hepatocytes in liver andvacuolation of proximal tubular cell inkidneys) Developmental NOAEL is 100 mg/kg bw/day LOAEL is 500 mg/kg bw/day, based on the increased incidence of cervical rib VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 PO 00000 Frm 00048 Fmt 4700 Sfmt 4700 E:\FR\FM\31AUR1.SGM 31AUR1 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations 51607 TABLE 1.—SUBCHRONIC, CHRONIC AND OTHER TOXICITY OF FLONICAMID—Continued Guideline No. Study Type Dose Levels Results 870.3700 Prenatal developmentaltoxicity (rabbits) 0, 2.5, 7.5, or 25 mg/ kg/day Maternal NOAEL is 7.5 mg/kg/day LOAEL is 25 mg/kg, based on decreased bodyweights, body weight gains, and food consumption Developmental NOAEL is ≥ 25 mg/kg/day LOAEL is not established 870.3800 Reproduction and fertility effects (rats) 0, 50, 300, or 1,800 ppm(0/0, 3.7/4.4, 22.3/26.5, and132.9/ 153.4 mg/kg bw/day [M/F] Parental NOAEL is 50 ppm (equivalent to 3.7/4.4mg/kg/ day [M/F] LOAEL is 300 ppm (equivalent to 22.3/26.5mg/ kg/day [M/F] based on increased relativekidney weight and hyaline droplet depositionin the proximal tubules of the kidneys in themales and increased blood serum LH levels inthe F1 females Offspring NOAEL is 300 ppm (equivalent to 22.3/26.5mg/ kg/day [M/F]. LOAEL is 1,800 ppm(equivalent to 132.9/153.4 mg/kg/day [M/ F]based on decreased absolute and relative tobody uterus weights and delayed sexualmaturation in the F1 females Reproductive Performance NOAEL is 1,800 ppm (equivalent to 132.9/ 153.4mg/kg/day [M/F] LOAEL for reproductive performance was notobserved 870.4100 Chronic toxicity (dogs) 0, 3, 8, or 20 mg/kg/ day NOAEL is 8 mg/kg/day LOAEL is 20 mg/kg/day, based on acute clinical signs(vomiting, mostly within the first week), clinical pathology at 12 months (higher reticulocytes counts) in males and females 870.4200 Carcinogenicity (mice) 0, 250, 750, or 2250 ppm(0/0, 29/38, 88/ 112, or261/334 mg/ kg/day [M/F] NOAEL was not established LOAEL is 250 ppm (equivalent to 29/38mg/kg/ day [M/F]), based on minimal tomoderate centrilobular hepatocellularhypertrophy, minimal to severeextramedullary hematopoiesis, minimal tomoderate pigment deposition in the sternalbone marrow, and increased incidence of tissuemasses/nodules in the lungs in the males, andminimal to moderate decreased cellularity inthe femoral bone marrow andhyperplasia/hypertrophy of the epithelial cellsof the terminal bronchioles of the females At the doses tested, the carcinogenic potentialof IKI-220 (flonicamid) is positive at 250 ppmin males and females based on the increasedincidence of alveolar/bronchiolar adenomas,carcinomas, and combinedadenomas/carcinomas. Dosing was consideredadequate based on increased incidence of tissuemasses/nodules in the lungs and microscopicfindings in the liver, spleen, bone marrow, andlungs. However, data were providedsuggesting this effect is specific to sensitivestrains of mice Carcinogenic in mice VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 PO 00000 Frm 00049 Fmt 4700 Sfmt 4700 E:\FR\FM\31AUR1.SGM 31AUR1 51608 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations TABLE 1.—SUBCHRONIC, CHRONIC AND OTHER TOXICITY OF FLONICAMID—Continued Guideline No. Study Type Dose Levels Results 870.4200 Carcinogenicity (mice) 0, 10, 25, 80, 250 ppmmales: 0, 1.20, 3.14, 10.0,30.3 mg/ kg/day; females: 0,1.42, 3.67, 11.8, 36.3 mg/kg/day NOAEL is 80 ppm (equivalent to 10/12mg/kg/ day in males/females) LOAEL is 250 ppm (equivalent to 30/36mg/kg/ day in males/females) based on lungmasses and terminal bronchiole epithelial cellhyperplasia/hypertrophy in both sexes At the doses tested, the carcinogenic potentialof IKI-220 (flonicamid) is positive in males andfemales based on the incidences ofalveolar/bronchiolar adenomas, carcinomas,and combined adenomas and/or carcinomas. Dosing was consideredadequate based on lung masses and terminal bronchiole epithelialcell hyperplasia/hypertrophy in both sexes Carcinogenic in mice 870.4300 Combined Chronic/carcinogenicity (rats) 0, 50 (males), 100 (males),200, 1,000, or 5,000 (females) ppm (0/0, 1.84,3.68, 7.32/8.92, 36.5/44.1, and 219 mg/kg/day [M/F] NOAEL is 200 ppm (equivalent to 7.32/8.92mg/ kg/day in males/females) LOAEL is 1,000 ppm (equivalent to 36.5/ 44.1mg/kg/day in males/females) based ondecreased body weights and body weight gains,and increased incidences of keratitis in malesand striated muscle fiber atrophy in females At the high dose there was an incidence (12%)of nasolacrimal duct squamous cell carcinomasslightly outside the historical control range (0-10%) in male rats. A correlation between theincidence of inflammation and the fluctuatingincidence of nasal tumors was made acrossdose groups. EPA did not consider thenasolacrimal duct tumors to be treatment-related Female rats had a significant increasing trendin nasolacrimal duct squamous cell carcinomasat <0.05, and at the high dose was slightlyabove the historical control mean (0.8%) andrange (0-4%). EPA considered the nasolacrimal duct squamouscell carcinomas to be possibly treatment related, but that a clearassociation with treatment could not be made 870.5100 Bacterial reverse mutation 61.7 to 5,000 µg/plate +/-S9 Negative 870.5100 Bacterial system, mammalian activationgene mutation 33 to 5,000 µg/plate +/S9 Negative for metabolite TFNA 870.5100 Bacterial system, mammalian activationgene mutation 33 to 5,000 ug/plate +/S9 Negative for metabolite TFNA-AM 870.5100 Bacterial system, mammalian activationgene mutation 33 to 5,000 ug/plate +/S9 Negative for metabolite TFNG-AM 870.5100 Bacterial system, mammalian activationgene mutation 33 to 5,000 µg/plate +/S9 Negative for metabolite TFNA-OH 870.5100 Bacterial system,mammalian activation gene mutation 5 to 5000 ug/plate +/S9 Negative for metabolite TFNG VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 PO 00000 Frm 00050 Fmt 4700 Sfmt 4700 E:\FR\FM\31AUR1.SGM 31AUR1 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations 51609 TABLE 1.—SUBCHRONIC, CHRONIC AND OTHER TOXICITY OF FLONICAMID—Continued Guideline No. Study Type Dose Levels Results 870.5300 In vitro mammalian cellgene mutation 28.3 to 2,290 µg/mL initialtest, and 143 to 2,290µg/mL repeat Negative 870.5375 In vitro Cytogenetics 573, 1145 and 2290 µg/mL Negative 870.5395 In vivo cytogenetic(micronucleus) test in mice Twice orally by intragastricgavage at doses of 250, 500and 1,000 mg/kg/ day formales and 125, 250 and 500mg/ kg/day for females Negative Non-guideline Other genotoxicity, in vivo Comet assay Single doses of 375, 750 and 1,500 mg/kg Was not positive for nuclear migration up to1,500 mg/kg Non-guideline Unscheduled DNA synthesis Once orally at 600 and 2,000 mg/kg Is not genotoxic in hepatocytes from treated rats 870.6200 Acute neurotoxicityscreening battery (rats) 0, 100, 300, 600 (males), or 1,000 mg/ kg/day NOAEL is 600 mg/kg in males and 300 mg/ kgin females LOAEL is 1,000 mg/kg based on mortality andsigns of toxicity (decreased motor activity,tremors, impaired respiration, and impairedgait) in males This acute neurotoxicity study is unacceptablebecause interval motor activity data were notprovided as specified according to guidelines,FOB handling and open-field observationswere incomplete, and positive data providedwere from a lab other than the performing labfor this study. This study is not required forthis risk assessment and additional informationis not required 870.6200 Subchronic neurotoxicity screeningbattery (rats) 0, 200, 1000, or 10,000 ppm(0/0, 13/16, 67/ 81, or625/722 mg/kg/ day [M/F] NOAEL is 200/1,000 ppm (equivalent to 13/ 81mg/kg/day [M/F] LOAEL is 1,000/10,000 ppm (equivalent to67/ 722 mg/kg/day [M/F] based on decreasedmotor activity, rearing, and foot splay inmales, decreased body weights, body weightgains, and food consumption in males andfemales 870.7485 Metabolism andpharmacokinetics (rats) Pilot excretion study, singleoral dose 0.85 or 21 mg/kgand pilot pharmacokineticstudy, single oral dose of 2or 50 mg/kg IKI-220 (flonicamid) was rapidly absorbed andexcreted with no apparent differences betweenthe sexes. By 48 hours after treatment, 93%of the administered dose had been eliminatedand by 168 hours ∼96% was eliminated. Theprimary route of elimination was the urine,accounting for ∼90% of the dose. The feces oftreated rats accounted for ∼5% of theadministered dose, with no significant amountsof radiolabel detected in expired air of eithersex. After 168 hours of a single high or lowdose of the test material, <3% of theradioactivity was recovered in the carcass and<0.05% in the blood, irrespective of dose orsex The pharmacokinetic parameters were alsosimilar between the dose levels (2 and 50mg/kg) and sexes. The radiolabel was rapidlyabsorbed and excreted. The apparent plasmahalf-life (TW) was 4.8-6.0 hours and theelimination followed first order kinetics. Thetime of maximum plasma concentration(Tmax) for individual animals ranged from0.25 to 1 hour after treatment (with a mean foreach group of 0.3-0.6 hours) VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 PO 00000 Frm 00051 Fmt 4700 Sfmt 4700 E:\FR\FM\31AUR1.SGM 31AUR1 51610 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations TABLE 1.—SUBCHRONIC, CHRONIC AND OTHER TOXICITY OF FLONICAMID—Continued Guideline No. Study Type 870.7485 Dose Levels Metabolism and pharmacokinetics (rats) B. Toxicological Endpoints For hazards that have a threshold below which there is no appreciable risk, the dose at which no adverse effects are observed (the NOAEL) from the toxicology study identified as appropriate for use in risk assessment is used to estimate the toxicological level of concern (LOC). However, the lowest dose at which adverse effects of concern are identified (the LOAEL) is sometimes used for risk assessment if no NOAEL was achieved in the toxicology study selected. An uncertainty factor (UF) is applied to reflect uncertainties inherent in the extrapolation from laboratory animal data to humans and in the variations in sensitivity among members of the human population as well as other unknowns. An UF of 100 is routinely used, 10X to account for interspecies differences and 10X for intraspecies differences. Three other types of safety or uncertainty factors may be used: ‘‘Traditional uncertainty factors;’’ the Results 2 or 400 mg/kg Appears that the overall recovery ofradioactive dose from all group was 94-99% by168 hours post-dose. Absorption was rapidand extensive, detected in plasma within 10minutes of dosing, with maximum plasmaconcentrations within 24-54 minutes. By 168hours post-dose, total urinary excretion was72-78%, cage rinse was 10-21%, and fecalexcretion was 4-7% dose. Parent (IKI-220)(flonicamid) and 9 metabolites accounted for80-94% of the dose for all groups. Parent wasdetected primarily in the urine, 46-73% of thedose in excreta in all groups. The primarymetabolite was 4trifluoromethylnicotinamide(TFNA-AM), 1827% dose in all dose groups,along with minor amounts of TFNA-AM N-oxide (1-4% dose).Other metabolites in urine and feces were detected atless than or equal to 2.5% of the dose.IKI-220 (flonicamid) was excreted primarily unchangedin the urine, but biotransformation of IKI-220(flonicamid) in rats included nitrile hydrolysis,N-oxidation, hydroxylation of the pyridine ring and amidehydrolysis ‘‘special FQPA safety factor;’’ and the ‘‘default FQPA safety factor’’ By the term ‘‘traditional uncertainty factor,’’ EPA is referring to those additional factors used prior to FQPA passage to account for database deficiencies. These traditional uncertainty factors have been incorporated by the FQPA into the additional safety factor for the protection of infants and children. The term ‘‘Special FQPA safety factor refers to those safety factors that are deemed necessary for the protection of infants and children, primarily as a result of the FQPA.’’ The ‘‘default FQPA safety factor’’ is the additional 10X safety factor that is mandated by the statute unless it is decided that there are reliable data to choose a different additional factor (potentially a traditional uncertainty factor or a special FQPA safety factor). For dietary risk assessment (other than cancer) the Agency uses the UF to calculate an acute or chronic reference dose (acute RfD or chronic RfD) where the RfD is equal to the NOAEL divided by an UF of 100 to account for interspecies and intraspecies differences and any traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF). Where a special FQPA safety factor or the default FQPA safety factor is used, this additional safety factor is applied to the RfD by dividing the RfD by such additional factor. The acute or chronic Population Adjusted Dose (aPAD or cPAD) is a modification of the RfD to accommodate this type of safety factor. For non-dietary risk assessments (other than cancer) the UF is used to determine the LOC. For example, when 100 is the appropriate UF (10X to account for interspecies differences, and 10X for intraspecies differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to exposure (margin of exposure (MOE) = NOAEL/exposure) is calculated and compared to the LOC. A summary of the toxicological dose and endpoints for flonicamid used for human risk assessment is shown in Table 2 of this unit: TABLE 2.—TOXICOLOGICAL DOSES AND ENDPOINTS FOR FLONICAMID HUMAN HEALTH RISK ASSESSMENTS Acute dietary VerDate Aug<18>2005 Special FQPA SF* andLevel of Concern for Risk Assessment Dose Used in RiskAssessment, UF Exposure Scenario None 16:14 Aug 30, 2005 Jkt 205001 FQPA SF = NA aPAD = NA PO 00000 Frm 00052 Fmt 4700 Sfmt 4700 Study and Toxicological Effects Quantitative risk assessment is notrequired since there are no acute dietarytoxicity concerns E:\FR\FM\31AUR1.SGM 31AUR1 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations 51611 TABLE 2.—TOXICOLOGICAL DOSES AND ENDPOINTS FOR FLONICAMID HUMAN HEALTH RISK ASSESSMENTS—Continued Dose Used in RiskAssessment, UF Special FQPA SF* andLevel of Concern for Risk Assessment Study and Toxicological Effects NOAEL = 3.7 mg/kg/day UF = 100 Chronic RfD = 0.04mg/kg/ day FQPA SF = 1 aPAD = chronic RfD/ FQPA SF= 0.04 mg/ kg/day 2–Generation Reproduction rat Parental LOAEL = 22 mg/kg/day basedon increased kidney weights, kidney hyaline deposition, increased blood serum LH (F1 females) Exposure Scenario Chronic dietary Cancer Suggestive evidence of carcinogenic potential UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable C. Exposure Assessment 1. Dietary exposure from food and feed uses. Tolerances are being proposed for the combined residues of flonicamid and its metabolites, in or on a variety of raw agricultural commodities. Risk assessments were conducted by EPA to assess dietary exposures from flonicamid and its metabolites in food as follows: i. Acute exposure. Quantitative acute dietary exposure and risk assessments are performed for a food-use pesticide, if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1–day or single exposure. No such effects were identified in the toxicological studies for flonicamid; therefore, a quantitative acute dietary exposure assessment is unnecessary. ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCIDTM Version 2), which incorporates food consumption data as reported by respondents in the USDA 1994–1996 and 1998 Nationwide Continuing Surveys of Food Intake by Individuals (CSFII), and accumulated exposure to the chemical for each commodity. The following assumptions were made for the chronic exposure assessments: 100% crop treated, tolerance level residues, and drinking water estimated concentration of 0.94 parts per billion (ppb). 2. Dietary exposure from drinking water. The Agency lacks sufficient monitoring exposure data to complete a comprehensive dietary exposure analysis and risk assessment for flonicamid and its metabolites in drinking water. Because the Agency does not have comprehensive monitoring data, drinking water concentration estimates are made by reliance on simulation or modeling taking into account data on the physical VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 characteristics of flonicamid and its metabolites. The Agency uses the Generic Estimated Environmental Concentration (GENEEC) or the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS) to estimate pesticide concentrations in surface water and Screening Concentrations in Groundwater (SCI-GROW), which predicts pesticide concentrations in ground water. In general, EPA will use GENEEC (a Tier 1 model) before using PRZM/EXAMS to estimate pesticide concentrations (a Tier 2 model) for a screening-level assessment for surface water. The GENEEC model is a subset of the PRZM/EXAMS model that uses a specific high-end runoff scenario for pesticides. GENEEC incorporates a farm pond scenario, while PRZM/EXAMS incorporate an index reservoir environment in place of the previous pond scenario. The PRZM/EXAMS model includes a percent crop area factor as an adjustment to account for the maximum percent crop coverage within a watershed or drainage basin. None of these models include consideration of the impact processing (mixing, dilution, or treatment) of raw water for distribution as drinking water would likely have on the removal of pesticides from the source water. The primary use of these models by the Agency at this stage is to provide a screen for sorting out pesticides for which it is unlikely that drinking water concentrations would exceed human health levels of concern. In order to fully implement the requirements of FQPA, EPA determined that chronic estimated drinking water concentrations (EDWCs) can be used directly in chronic dietary exposure assessments to calculate aggregate dietary (food + water) risk. This is done by using the relevant PRZM-EXAMS value as a residue for water (all sources) in the dietary exposure assessment. The principal advantage of this approach is that the actual individual body weight PO 00000 Frm 00053 Fmt 4700 Sfmt 4700 and water consumption data from the CSFII are used, rather than assumed weights and consumption for broad age groups. This refinement has been used for the flonicamid chronic aggregate risk assessment for surface water. Based on the PRZM/EXAMS and SCIGROW models, the EDWCs of combined residues of flonicamid and its metabolites for chronic exposures are estimated to be 0.94 ppb for surface water and 0.00137 ppb for ground water. 3. From non-dietary exposure. The term ‘‘residential exposure’’ is used in this document to refer to nonoccupational, non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Flonicamid is not registered for use on any sites that would result in residential exposure. 4. Cumulative effects from substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of the FFDCA 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 flonicamid and any other substances, and flonicamid does not appear to produce a toxic metabolite produced by other substances. EPA considered that there might be a common mechanism among flonicamid and other pesticides. EPA concluded that the evidence did not support a finding of common mechanism for flonicamid and other pesticides. For the purposes of this tolerance action, therefore, EPA has not assumed that flonicamid has a common mechanism of toxicity with other E:\FR\FM\31AUR1.SGM 31AUR1 51612 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/ pesticides/cumulative/. D. Safety Factor for Infants and Children 1. In general. Section 408 of FFDCA provides that EPA shall apply an additional tenfold margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the data base on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. Margins of safety are incorporated into EPA risk assessments either directly through use of a MOE analysis or through using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk to humans. In applying this provision, EPA either retains the default value of 10X when reliable data do not support the choice of a different factor, or, if reliable data are available, EPA uses a different additional safety factor value based on the use of traditional uncertainty factors and/or special FQPA safety factors, as appropriate. 2. Prenatal and postnatal sensitivity. There was no evidence for quantitative or qualitative susceptibility following oral or dermal exposures to rats in utero or oral exposure to rabbits in utero. Following oral exposures to rats, developmental effects were seen only in the presence of maternal toxicity. No developmental effects were seen in rabbits. The degree of concern for prenatal and/or postnatal susceptibility is low due to the lack of evidence of qualitative and quantitative susceptibility. This is because developmental effects were only seen in one species, only at the maternal toxicity dose, and effects seen in offspring were not more severe than those seen in the maternal toxicity. Thus, neither qualitative nor quantitative susceptibility issues are of concern for flonicamid. The database for required developmental and reproductive studies is complete, thus there are no residual uncertainties. 3. Conclusion. The FQPA Safety Factor is reduced to 1X because: VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 i. There is a complete toxicity database; ii. There is a lack of susceptibility evidence in the developmental studies and reproductive study (The effects seen in offspring were mild and occurred only in one species.); iii. The dietary food exposure assessment utilizes proposed tolerance level or higher residues and 100% CT information for all commodities; and iv. The dietary drinking water assessment (Tier 1 estimates) utilizes values generated by model and associated modeling parameters which are designed to provide conservative, health protective, high-end estimates of water concentrations. E. Aggregate Risks and Determination of Safety 1. Acute risk. No acute risk is expected for the following reasons: No acute toxicity endpoint was identified. There was no endpoint noted in the database from a single dose exposure that could be used for risk assessment. This included the acute neurotoxicity and developmental toxicity studies as well as other short- and long-term studies. Body weight decreases were consider inappropriate for this acute endpoint since in these studies they occur later then the acute time interval. The observed vomiting in either the acute or subchronic dog studies occurred without manifestations of any other acute clinical signs or related pathology. Thus acute clinical effects seen in the dog studies were considered not appropriate. The acute neurotoxicity study was also not appropriate for the general population since the effects observed only occurred in the high doses tested where mortality was also observed, and therefore the neurotoxicity signs were probably part of the death response. While death can be an acute response, the dose at which death occurred was in EPA’s judgement, so high that it is unlikely to happen. In addition, the acute neurotoxicity study did not have all the required observations. The effects observed in the developmental studies were not attributable to an acute response, and therefore the developmental studies were not used for an acute endpoint for females of reproductive age. Thus, an acute dietary endpoint was not considered appropriate. 2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that exposure to flonicamid and its metabolites from food and drinking water will utilize 11% of the cPAD for the U.S. population, 15% of the cPAD for all infants <1 year old, and 25% of PO 00000 Frm 00054 Fmt 4700 Sfmt 4700 the cPAD for children 1-2 years old. There are no residential uses for flonicamid that result in chronic residential exposure to flonicamid. 3. Short-term and intermediate term risk. Short-term aggregate exposure takes into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Intermediate-term aggregate exposure takes into account residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Flonicamid is not registered for use on any sites that would result in residential exposure. Therefore, the aggregate risk is the sum of the risk from food and water, which do not exceed the Agency’s level of concern. 4. Aggregate cancer risk for U.S. population. In assessing the carcinogenic potential of flonicamid, EPA took into account the following weight-of-the-evidence considerations: i. Flonicamid is not mutagenic. ii. The treatment-related CD-1 mouse lung tumors (benign and malignant) which occurred in both sexes were due to an established mitogenic mode of action that occurred in a susceptible mouse strain with a high background. A clear species difference was observed between mice and rats in the incidence of lung tumors and the BrdU Index studies. (Bromodeoxyuridine (BrdU) Index studies are used to quantify rates of cell proliferation). No tumors were seen in the lungs of rats. The flonicamid induced increase in the BrdU Index appears to be related to the different sensitivity of strains of mice, with the CD-1 mice being a relatively sensitive strain. iii. The only other tumor response was nasolacrimal duct tumors which occurred in female rats at the high dose which were considered to be possibly treatment-related, but a clear association with treatment could not be made. Unlike male rats, the nasal tumor response in females could not be clearly associated with spontaneous inflammation related to malocclusion of incisor teeth, due to the low incidence of both the neoplastic and nonneoplastic lesions. Given these findings in the cancer and mutagenicity studies, EPA regards the carcinogenic potential of flonicamid as very low and concludes that it poses no greater than a negligible cancer risk to humans. 5. Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population, and to infants and children from aggregate exposure to flonicamid residues. E:\FR\FM\31AUR1.SGM 31AUR1 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations IV. Other Considerations A. Analytical Enforcement Methodology Adequate enforcement methods are available to enforce the proposed tolerances of flonicamid and the major metabolites in plants and livestock. The proposed method for plants uses a LC/ MS/MS (FMC No. P-3561M) to determine the residues of flonicamid and its major metabolites, TFNA-AM (4trifluoromethylnicotinamide), TFNA (4trifluoromethylnicotinic acid), and TFNG [N-(4trifluoromethylnicotinoyl)glycine]. The reported LOQ was 0.01 ppm and the reported LOD was 0.005 ppm for peach, potato, processed commodities of apples, plums, potatoes, and tomatoes. The reported LOQ was 0.02 ppm and the LOD was 0.01 ppm for each analyte in/on wheat; cotton seed, hulls, and refined oil. The method was adequately validated by an independent laboratory. For livestock, three methods were proposed: LC/MS/MS method (RCC No. 844743) for residues in eggs and livestock tissues, LC/MS method (RCC No. 842993) for residues in milk, and LC/MS/MS method (FMC P3580) which include an acid hydrolysis step for residues in cattle muscle, kidney and liver. The three livestock methods recommend the use of calibration standards, prepared by using control matrix extracts for all or some of the analyze/matrix combinations to remove matrix enhancement effects. The methods were adequately validated by an independent laboratory. These methods may be used for the determination of residues of flonicamid and its metabolites TFNA-AM, TFNG, and TFNA. The validated LOQ was 0.01 ppm and LOD was 0.005 ppm for methods 844743 and 842993; the reported validated LOQ was 0.025 ppm and the LOD was 0.005 ppm for method FMC P3580. Enforcement methodology may be requested from: Chief, Analytical Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755–5350; telephone number: (410) 305–2905; e-mail address: residuemethods@epa.gov. B. International Residue Limits No Codex, Mexican or Canadian MRLs or tolerances have been established. Therefore no compatibility questions exist with respect to Codex. C. Response to Comments EPA received one comment from the National Cotton Council, which stated that it supports ISK Bioscience’s request for the establishment of tolerances in the listed food and feed items. In today’s VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 action, EPA is responding affirmatively to this comment. V. Conclusion Therefore, tolerances are established for the combined residues of flonicamid [N-(cyanomethyl)-4-trifluoromethyl)-3pyridinecarboxamide], and its metabolites TFNA [4trifluoromethylnicotinic acid], TFNAAM [4-trifluoromethylnicotinamide] and TFNG [N-(4trifluoromethylnicotinoyl)glycine] in or on the crops at tolerance levels listed in Unit III. Tolerances are established for the combined residues of flonicamid [N(cyanomethyl)-4-(trifluoromethyl)-3pyridinecarboxamide], and its metabolites TFNA [4trifluoromethylnicotinic acid] and TFNA-AM [4trifluoromethylnicotinamide] in or on the livestock commodities at tolerance levels listed in Unit III. VI. Objections and Hearing Requests Under section 408(g) of FFDCA, as amended by FQPA, any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. The EPA procedural regulations which govern the submission of objections and requests for hearings appear in 40 CFR part 178. Although the procedures in those regulations require some modification to reflect the amendments made to FFDCA by FQPA, EPA will continue to use those procedures, with appropriate adjustments, until the necessary modifications can be made. The new section 408(g) of FFDCA provides essentially the same process for persons to ‘‘object’’ to a regulation for an exemption from the requirement of a tolerance issued by EPA under new section 408(d) of FFDCA, as was provided in the old sections 408 and 409 of FFDCA. However, the period for filing objections is now 60 days, rather than 30 days. A. What Do I Need to Do to File an Objection or Request a Hearing? You must file your objection or request a hearing on this regulation in accordance with the instructions provided in this unit and in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number OPP–2005–0217 in the subject line on the first page of your submission. All requests must be in writing, and must be mailed or delivered to the Hearing Clerk on or before October 31, 2005. 1. Filing the request. Your objection must specify the specific provisions in the regulation that you object to, and the PO 00000 Frm 00055 Fmt 4700 Sfmt 4700 51613 grounds for the objections (40 CFR 178.25). If a hearing is requested, the objections must include a statement of the factual issue(s) on which a hearing is requested, the requestor’s contentions on such issues, and a summary of any evidence relied upon by the objector (40 CFR 178.27). Information submitted in connection with an objection or hearing request may be claimed confidential by marking any part or all of that information as CBI. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. A copy of the information that does not contain CBI must be submitted for inclusion in the public record. Information not marked confidential may be disclosed publicly by EPA without prior notice. Mail your written request to: Office of the Hearing Clerk (1900L), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001. You may also deliver your request to the Office of the Hearing Clerk in Suite 350, 1099 14th St., NW., Washington, DC 20005. The Office of the Hearing Clerk is open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Office of the Hearing Clerk is (202) 564–6255. 2. Copies for the Docket. In addition to filing an objection or hearing request with the Hearing Clerk as described in Unit VI.A., you should also send a copy of your request to the PIRIB for its inclusion in the official record that is described in ADDRESSES. Mail your copies, identified by docket ID number OPP–2005–0217, to: Public Information and Records Integrity Branch, Information Resources and Services Division (7502C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001. In person or by courier, bring a copy to the location of the PIRIB described in ADDRESSES. You may also send an electronic copy of your request via email to: opp-docket@epa.gov. Please use an ASCII file format and avoid the use of special characters and any form of encryption. Copies of electronic objections and hearing requests will also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format. Do not include any CBI in your electronic copy. You may also submit an electronic copy of your request at many Federal Depository Libraries. B. When Will the Agency Grant a Request for a Hearing? A request for a hearing will be granted if the Administrator determines that the material submitted shows the following: E:\FR\FM\31AUR1.SGM 31AUR1 51614 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations There is a genuine and substantial issue of fact; there is a reasonable possibility that available evidence identified by the requestor would, if established resolve one or more of such issues in favor of the requestor, taking into account uncontested claims or facts to the contrary; and resolution of the factual issue(s) in the manner sought by the requestor would be adequate to justify the action requested (40 CFR 178.32). VII. Statutory and Executive Order Reviews This final rule establishes a tolerance under section 408(d) of FFDCA in response to a petition submitted to the Agency. The Office of Management and Budget (OMB) has exempted these types of actions from review under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993). Because this rule has been exempted from review under Executive Order 12866 due to its lack of significance, this rule is not subject to Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001). This final rule does not contain any information collections subject to OMB approval under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or contain any unfunded mandate as described under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104–4). Nor does it require any special considerations under Executive Order 12898, entitled Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations (59 FR 7629, February 16, 1994); or OMB review or any Agency action under Executive Order 13045, entitled Protection of Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does not involve any technical standards that would require Agency consideration of voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act of 1995 (NTTAA), Public Law 104–113, section 12(d) (15 U.S.C. 272 note). Since tolerances and exemptions that are established on the basis of a petition under section 408(d) of FFDCA, such as the tolerance in this final rule, do not require the issuance of a proposed rule, the requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply. In addition, the Agency has determined that this action will not have a substantial direct effect on States, on the relationship between VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 the national government and the States, or on the distribution of power and responsibilities among the various levels of government, as specified in Executive Order 13132, entitled Federalism (64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to develop an accountable process to ensure ‘‘meaningful and timely input by State and local officials in the development of regulatory policies that have federalism implications.’’ ‘‘Policies that have federalism implications’’ is defined in the Executive Order to include regulations that have ‘‘substantial direct effects on the States, on the relationship between the national government and the States, or on the distribution of power and responsibilities among the various levels of government.’’ This final rule directly regulates growers, food processors, food handlers and food retailers, not States. This action does not alter the relationships or distribution of power and responsibilities established by Congress in the preemption provisions of section 408(n)(4) of FFDCA. For these same reasons, the Agency has determined that this rule does not have any ‘‘tribal implications’’ as described in Executive Order 13175, entitled Consultation and Coordination with Indian Tribal Governments (65 FR 67249, November 6, 2000). Executive Order 13175, requires EPA to develop an accountable process to ensure ‘‘meaningful and timely input by tribal officials in the development of regulatory policies that have tribal implications.’’ ‘‘Policies that have tribal implications’’ is defined in the Executive Order to include regulations that have ‘‘substantial direct effects on one or more Indian tribes, on the relationship between the Federal Government and the Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes.’’ This rule will not have substantial direct effects on tribal governments, on the relationship between the Federal Government and Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes, as specified in Executive Order 13175. Thus, Executive Order 13175 does not apply to this rule. VIII. Congressional Review Act The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the Small Business Regulatory Enforcement Fairness Act of 1996, generally provides that before a rule may take effect, the agency promulgating the rule must submit a rule report, which includes a PO 00000 Frm 00056 Fmt 4700 Sfmt 4700 copy of the rule, to each House of the Congress and to the Comptroller General of the United States. EPA will submit a report containing this rule and other required information to the U.S. Senate, the U.S. House of Representatives, and the Comptroller General of the United States prior to publication of this final rule in the Federal Register. This final rule is not a ‘‘major rule’’ as defined by 5 U.S.C. 804(2). List of Subjects in 40 CFR Part 180 Environmental protection, Administrative practice and procedure, Agricultural commodities, Pesticides and pests, Reporting and recordkeeping requirements. Dated: August 19, 2005. Lois A. Rossi, Acting Director, Office of Pesticide Programs. Therefore, 40 CFR chapter I is amended as follows: I PART 180—AMENDED 1. The authority citation for part 180 continues to read as follows: I Authority: 21 U.S.C. 321(q), 346a and 371. 2. Section 180.613 is added to read as follows: I § 180.613 Flonicamid; tolerances for residues. (a) General. (1) Tolerances are established for the combined residues of flonicamid [N-(cyanomethyl)-4(trifluoromethyl)-3pyridinecarboxamide] and its metabolites TFNA [4trifluoromethylnicotinic acid], TFNAAM [4-trifluoromethylnicotinamide] TFNG [N-(4trifluoromethylnicotinoyl)glycine] in or on the following raw agricultural commodities: Commodity Cotton, gin byproducts .................... Cotton, hulls .......... Cotton, meal ......... Cotton, undelinted seed .................. Fruit, pome, group 11 ...................... Fruit, stone, group 12 ...................... Potato ................... Potato, granular/ flakes ................. Spinach ................. Tomato, paste ....... Tomato, puree ...... Vegetable, cucurbit, group .. Vegetable, fruiting, group ................. E:\FR\FM\31AUR1.SGM 31AUR1 Parts per million 6.0 2.0 1.0 0.50 0.20 0.60 0.20 0.40 9.0 2.0 0.50 0.40 0.40 Federal Register / Vol. 70, No. 168 / Wednesday, August 31, 2005 / Rules and Regulations Commodity Parts per million Vegetable, leafy except Brassica group 4, except spinach .............. 4.0 (2) Tolerances are established for combined residues of flonicamid [N(cyanomethyl)-4-(trifluoromethyl)-3pyridinecarboxamide], and its metabolites TFNA [4trifluoromethylnicotinic acid], TFNAAM [4-trifluoromethylnicotinamide] in or on the following raw agricultural commodities: Commodity Parts per million Cattle, fat .............. Cattle, meat .......... Cattle, meat byproducts ............ Egg ....................... Goat, fat ................ Goat, meat ............ Goat, meat byproducts .................... Horse, fat .............. Horse, meat .......... Horse, meat byproducts ............ Milk ....................... Poultry, fat ............ Poultry, meat ........ Poultry, meat byproducts ............ Sheep, fat ............. Sheep, meat ......... Sheep, meat by products ............ 0.02 0.05 0.08 0.03 0.02 0.05 0.08 0.02 0.05 0.08 0.02 0.02 0.02 0.02 0.02 0.05 0.08 (b) Section 18 emergency exemptions. [Reserved] (c) Tolerances with regional registrations. [Reserved] (d) Indirect or inadvertent residues. [Reserved] [FR Doc. 05–17128 Filed 8–30–05; 8:45 am] BILLING CODE 6560–50–S ENVIRONMENTAL PROTECTION AGENCY I. General Information 40 CFR Part 180 [OPP–2005–0165; FRL–7719–8] Halosulfuron-methyl; Pesticide Tolerances for Emergency Exemptions Environmental Protection Agency (EPA). ACTION: Final rule. AGENCY: SUMMARY: This regulation establishes a time-limited tolerance for residues of halosulfuron-methyl in or on sweet potatoes. This action is in response to EPA’s granting of an emergency exemption under section 18 of the VerDate Aug<18>2005 16:14 Aug 30, 2005 Jkt 205001 Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) authorizing use of the pesticide on sweet potatoes. This regulation establishes a maximum permissible level for residues of halosulfuron-methyl in this food commodity. The tolerance will expire and is revoked on December 31, 2008. DATES: This regulation is effective August 31, 2005. Objections and requests for hearings must be received on or before October 31, 2005. ADDRESSES: To submit a written objection or hearing request follow the detailed instructions as provided in Unit VII. of the SUPPLEMENTARY INFORMATION. EPA has established a docket for this action under docket identification (ID) number OPP–2005– 0165. All documents in the docket are listed in the EDOCKET index at http:// www.epa.gov/edocket/. Although listed in the index, some information is not publicly available, i.e., Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the Internet and will be publicly available only in hard copy form. Publicly available docket materials are available either electronically in EDOCKET or in hard copy at the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1801 S. Bell St., Arlington, VA. This docket facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The docket telephone number is (703) 305–5805. FOR FURTHER INFORMATION CONTACT: Andrew Ertman, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460–0001; telephone number: (703) 308–9367; e-mail address: ertman.andrew@epa.gov. SUPPLEMENTARY INFORMATION: A. Does this Action Apply to Me? You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially affected entities may include, but are not limited to: • Crop production (NAICS code 111). • Animal production (NAICS code 112). • Food manufacturing (NAICS code 311). • Pesticide manufacturing (NAICS code 32532). This listing is not intended to be exhaustive, but rather provides a guide PO 00000 Frm 00057 Fmt 4700 Sfmt 4700 51615 for readers regarding entities likely to be affected by this action. Other types of entities not listed in this unit could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. If you have any questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT. B. How Can I Access Electronic Copies of this Document and Other Related Information? In addition to using EDOCKET (http:// www.epa.gov/edocket/), you may access this Federal Register document electronically through the EPA Internet under the ‘‘Federal Register’’ listings at http://www.epa.gov/fedrgstr/. A frequently updated electronic version of 40 CFR part 180 is available on E-CFR Beta Site Two at http:// www.gpoaccess.gov/ecfr/. II. Background and Statutory Findings EPA, on its own initiative, in accordance with sections 408(e) and 408(l)(6) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, is establishing a tolerance for residues of the herbicide halosulfuron-methyl, in or on sweet potatoes at 1.0 parts per million (ppm). This tolerance will expire and is revoked on December 31, 2008. EPA will publish a document in the Federal Register to remove the revoked tolerance from the Code of Federal Regulations (CFR). Section 408(l)(6) of FFDCA requires EPA to establish a time-limited tolerance or exemption from the requirement for a tolerance for pesticide chemical residues in food that will result from the use of a pesticide under an emergency exemption granted by EPA under section 18 of FIFRA. Such tolerances can be established without providing notice or period for public comment. EPA does not intend for its actions on FIFRA section 18 related tolerances to set binding precedents for the application of section 408 of FFDCA and the new safety standard to other tolerances and exemptions. Section 408(e) of FFDCA allows EPA to establish a tolerance or an exemption from the requirement of a tolerance on its own initiative, i.e., without having received any petition from an outside party. Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is ‘‘safe.’’ E:\FR\FM\31AUR1.SGM 31AUR1

Agencies

[Federal Register Volume 70, Number 168 (Wednesday, August 31, 2005)]
[Rules and Regulations]
[Pages 51604-51615]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-17128]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2005-0217; FRL-7731-6]


Flonicamid; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a tolerance for combined residues 
of flonicamid and its metabolites in or on certain plant and livestock 
commodities. ISK Biosciences requested this tolerance under the Federal 
Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality 
Protection Act of 1996 (FQPA).

DATES: This regulation is effective August 31, 2005. Objections and 
requests for hearings must be received on or before October 31, 2005.

ADDRESSES:  To submit a written objection or hearing request follow the 
detailed instructions as provided in Unit VI. of the SUPPLEMENTARY 
INFORMATION. EPA has established a docket for this action under Docket 
identification (ID) number OPP-2005-0217. All documents in the docket 
are listed in the EDOCKET index athttp://www.epa.gov/edocket. Although 
listed in the index, some information is not publicly available, i.e., 
CBI or other information whose disclosure is restricted by statute. 
Certain other material, such as copyrighted material, is not placed on 
the Internet and will be publicly available only in hard copy form. 
Publicly available docket materials are available either electronically 
in EDOCKET or in hard copy at the Public Information and Records 
Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 1801 S. 
Bell St., Arlington, VA. This docket facility is open from 8:30 a.m. to 
4 p.m., Monday through Friday, excluding legal holidays. The docket 
telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT:  Ann Sibold, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305-6502; e-mail address:sibold.ann@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does This Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS 111), e.g., agricultural workers; 
greenhouse, nursery, and floriculture workers; farmers.
     Animal production (NAICS 112), e.g., cattle ranchers and 
farmers, dairy cattle farmers, livestock farmers.
     Food manufacturing (NAICS 311), e.g., agricultural 
workers; farmers; greenhouse, nursery, and floriculture workers; 
ranchers; pesticide applicators.
     Pesticide manufacturing (NAICS 32532), e.g., agricultural 
workers; commercial applicators; farmers; greenhouse, nursery, and 
floriculture workers; residential users.
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed underFOR FURTHER INFORMATION CONTACT.

B. How Can I Access Electronic Copies of this Document and Other 
Related Information?

    In addition to using EDOCKET (http://www.epa.gov/edocket/), you may 
access this Federal Register document electronically through the EPA 
Internet under the ``Federal Register'' listings at http://www.epa.gov/
fedrgstr/. A frequently updated electronic version of 40 CFR part 180 
is available at E-CFR Beta Site Two at http://www.gpoaccess.gov/ecfr/. 
To access the OPPTS Harmonized Guidelines referenced in this document, 
go directly to the guidelines athttp://www.epa.gpo/opptsfrs/home/
guidelin.htm/.

II. Background and Statutory Findings

    In the Federal Register of May 23, 2003 (68 FR 28218) (FRL-7307-5), 
EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 
346a(d)(3), announcing the filing of a pesticide petition (PP 3F6552) 
by ISK Biosciences, 7470 Auburn Road, suite A, Concord, Ohio 44077. The 
petition requested that 40 CFR part 180 be amended by establishing a 
tolerance for the combined residues of the insecticide flonicamid, [N-
(cyanomethyl)-4-trifluoromethylnicotinamide] and its metabolites, TFNA, 
(4-trifluoromethylnicotinic acid), TFNA-AM, (4-
trifluoromethylnicotinamide) and TFNG, [N-(4-
trifluoromethylnicotinoyl)glycine] in or on the raw agricultural 
commodities: Celery, at 1.2 parts per million (ppm); cotton, at 0.5 
ppm; cotton, gin trash, at 6.0 ppm; cotton, hulls, at 1.0 ppm; cotton, 
meal, at 1.0 ppm; fruit, pome, group 11, at 0.2 ppm; fruit, stone, 
group 12, except plum and fresh prune plum, at 0.7 ppm; lettuce, head, 
at 1.0 ppm; lettuce, leaf, at 4.0 ppm; plum, at 0.1 ppm; potato, at 0.2 
ppm; potato, flakes, at 0.4 ppm; prune, fresh, at 0.1; spinach, at 9.0 
ppm; tomato, paste, at 2.0 ppm; tomato, puree, at 0.5 ppm; vegetable,

[[Page 51605]]

cucurbit, group 9, at 0.4 ppm; vegetable, fruiting, group 8, at 0.4 
ppm; by establishing tolerances for the combined residues of the 
insecticide flonicamid, [N-(cyanomethyl)-4-trifluoromethylnicotinamide] 
and its metabolite TFNA-AM, (4-trifluoromethylnicotinamide) in animal 
tissues and poultry meat byproducts:Cattle, fat, at 0.01 ppm; cattle, 
meat, at 0.04 ppm; eggs, at 0.02 ppm; goat, fat, at 0.01 ppm; goat, 
meat, at 0.04 ppm; hog, fat, at 0.01; hog, meat, at 0.01 ppm; horse, 
fat, at 0.01 ppm; horse, meat, at 0.04 ppm; milk, at 0.02 ppm; poultry, 
fat, at 0.01 ppm; poultry, meat, at 0.01 ppm; poultry, meat byproducts, 
at 0.01 ppm; sheep, fat, at 0.01 ppm; sheep, meat, at 0.04 ppm; by 
establishing tolerances for the combined residues of the insecticide 
flonicamid [N-(cyanomethyl)-4-trifluoromethylnicotinamide] and its 
metabolites TFNA, (4-trifluoromethylnicotinic acid) and TFNA-AM, (4- 
trifluoromethylnicotinamide) in the animal meat byproducts: cattle, 
meat byproducts, at 0.06 ppm; goat, meat byproducts, at 0.06 ppm; hog, 
meat byproducts, at 0.01 ppm; horse, meat byproducts, at 0.06 ppm; and 
sheep, meat byproducts, at 0.06 ppm. That notice included a summary of 
the petition prepared by ISK Biosciences, the registrant. One comment 
was received on the notice of filing. EPA's response to this comment is 
discussed in Unit IV.C.
    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue. . . 
.''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 of FFDCA and a complete 
description of the risk assessment process, see the final rule on 
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997, FRL-
5754-7)

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2) of FFDCA, for a tolerance for combined residues of flonicamid 
and its metabolites on various crop and livestock commodities at levels 
set forth in the list below.
    Tolerances for combined residues of flonicamid and its metabolites 
in/on crops and livestock commodities.
    1. Recommended tolerances for combined residues of flonicamid and 
its metabolites TFNA, TFNG and TFNA-AM in/on crops.
    Cotton, undelinted seed at 0.50 ppm
    Cotton, gin byproducts at 6.0 ppm
    Cotton, hulls at 2.0 ppm
    Cotton, meal at 1.0 ppm
    Fruit, pome, group 11 at 0.20 ppm
    Fruit, stone, group at 12 0.60 ppm
    Potato 0.20 at ppm
    Potato, granular/flakes at 0.40 ppm
    Spinach at 9.0 ppm
    Tomato, paste at 2.0 ppm
    Tomato, puree at 0.50 ppm
    Vegetable, cucurbit, group at 0.40 ppm
    Vegetable, fruiting, group at 0.40 ppm
    Vegetable, leafy except Brassica group 4, except spinach at 4.0 ppm
    2. Recommended tolerances for combined residues of flonicamid and 
its metabolites TFNA and TFNA-AM in/on livestock commodities.
    Cattle, fat at 0.02 ppm
    Cattle, meat at 0.05 ppm
    Egg at 0.03 ppm
    Goat, fat at 0.02 ppm
    Goat, meat at 0.05 ppm
    Horse, fat at 0.02 ppm
    Horse, meat at 0.05 ppm
    Milk at 0.02 ppm
    Poultry, fat at 0.02 ppm
    Poultry, meat at 0.02 ppm
    Poultry, meat byproducts at 0.02 ppm
    Sheep, fat at 0.02 ppm
    Sheep, meat at 0.05 ppm
    Cattle, meat byproducts at 0.08 ppm
    Goat, meat byproducts at 0.08 ppm
    Horse, meat byproducts at 0.08 ppm
    Sheep, meat byproducts at 0.08 ppm
    EPA's assessment of exposures and risks associated with 
establishing the tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. Specific information on the studies received and the nature 
of the toxic effects caused by flonicamid as well as the no observed 
adverse effect level (NOAEL) and the lowest observed adverse effect 
level (LOAEL) from the toxicity studies are discussed in Table 1 of 
this unit.

[[Page 51606]]



                         Table 1.--Subchronic, Chronic and Other Toxicity of Flonicamid
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           Guideline No.                   Study Type              Dose Levels                 Results
----------------------------------------------------------------------------------------------------------------
870.3100                             90-Day oral toxicity    0, 50 (males), 200,     NOAEL is 200 ppm (12.11 mg/
                                      rodents (rats)          1,000,2,000 (males),    kg/day) formales and 1,000
                                     28-day range-finding..   or 5,000(females) ppm   ppm (72.3 mg/kg/day)
                                                              (3.08, 12.11,60.0, or   forfemales
                                                              119.4 mg/kg/day,males  LOAELs were 1,000 ppm (60.0
                                                              and 14.52, 72.3,        mg/kg/day) formales based
                                                              or340.1 mg/kg/day,      on changes in the kidney
                                                              females)                (hyalinedeposition) and
                                                             0, 50 (males), 100,      5,000 ppm (340 mg/kg/day)
                                                              500, 1,000,5,000 or     forfemales based on kidney
                                                              10,000 (females)ppm     (hyaline deposition)and
                                                              (3.61, 7.47,            liver changes
                                                              36.45,73.8, or 353.4    (centrilobular
                                                              mg/kg/day,males and     hypertrophy)
                                                              8.36, 41.24,           NOAEL is 100 ppm (7.47 mg/
                                                              81.9,372.6, or 642 mg/  kg/day) for malesand 1,000
                                                              kg/day,females).        ppm (81.9 mg/kg/day) for
                                                                                      females.
                                                                                     LOAELs were 500 ppm (36.45
                                                                                      mg/kg/day) formales based
                                                                                      on changes in the kidney
                                                                                      (hyalinedeposition) and
                                                                                      5,000 ppm for females
                                                                                      (372.6mg/kg/day) based on
                                                                                      kidney
                                                                                      (hyalinedeposition), liver
                                                                                      changes
                                                                                      (centrilobularhypertrophy)
                                                                                      , hematological effects
                                                                                      (anemia)and clinical
                                                                                      chemistry (increased
                                                                                      cholesterol)
-------------------------------------------------------------------------------------
870.3100                             90-Day oral toxicity    0, 100, 1,000 or 7,000  NOAEL is 100 ppm (males:
                                      rodents (mice)          ppm(0, 15.25, 153.9     15.25 mg/kgbw/day,
                                                              or 1,069mg/kg bw/day    females: 20.10 mg/kg bw/
                                                              in males,and 0,         day)
                                                              20.10, 191.5, or       LOAEL is 1,000 ppm in
                                                              1,248mg/kg bw/day in    (males: 153.9 mg/kgbw/day;
                                                              females)                females: 191.5 mg/kg bw/
                                                                                      day) basedon
                                                                                      extramedullary
                                                                                      hematopoiesis of the
                                                                                      spleen
                                                                                     Many of the tissues/organs
                                                                                      recommended byGuideline
                                                                                      870.3100 were not
                                                                                      histologicallyexamined in
                                                                                      any dose group, but this
                                                                                      study isnot required and
                                                                                      serves as a range-
                                                                                      findingstudy for the mouse
                                                                                      carcinogenicity
                                                                                      study.Therefore, it is
                                                                                      classified as acceptable,
                                                                                      non-guideline study
-------------------------------------------------------------------------------------
870.3150                             90-Day oral toxicity    0, 3, 8, 20, or 50      NOAEL is 8 mg/kg/day in
                                      (nonrodents- dogs)      (females) mg/kg bw/     males and 20 mg/kg/day for
                                                              day                     female
                                                                                     LOAEL is 20 mg/kg/day in
                                                                                      males and 50 mg/kg/day in
                                                                                      females, based on acute
                                                                                      clinical signs in males
                                                                                      and females (vomiting,
                                                                                      first observed on Day 1
                                                                                      and last observed on Day
                                                                                      90), clinical pathology at
                                                                                      7 weeks (increased total
                                                                                      protein levels in males,
                                                                                      lower red blood cells and
                                                                                      higher reticulocytescounts
                                                                                      in females), increased
                                                                                      adrenal weights in males,
                                                                                      decreased thymusgland
                                                                                      weights in males, and
                                                                                      increased kidney tubular
                                                                                      vacuolation infemales at
                                                                                      study termination
-------------------------------------------------------------------------------------
870.3200                             28-Day dermal toxicity  0, 20, 150, or 1,000    NOAEL is 1,000 mg/kg/day
                                      (rats)                  mg/kg/day              LOAEL is >1,000 mg/kg/day
-------------------------------------------------------------------------------------
870.3700                             Prenatal developmental  0, 20, 100 or 500 mg/   Maternal
                                      toxicity (rats)         kg bw/day              NOAEL is 100 mg/kg bw/day
                                                                                     LOAEL is 500 mg/kg bw/day,
                                                                                      based onincreased liver
                                                                                      weight, and liver and
                                                                                      kidneypathological changes
                                                                                      (hypertrophy
                                                                                      ofcentrilobular
                                                                                      hepatocytes in liver
                                                                                      andvacuolation of proximal
                                                                                      tubular cell inkidneys)
                                                                                     Developmental
                                                                                     NOAEL is 100 mg/kg bw/day
                                                                                     LOAEL is 500 mg/kg bw/day,
                                                                                      based on the increased
                                                                                      incidence of cervical rib
-------------------------------------------------------------------------------------

[[Page 51607]]

 
870.3700                             Prenatal                0, 2.5, 7.5, or 25 mg/  Maternal
                                      developmentaltoxicity   kg/day                 NOAEL is 7.5 mg/kg/day
                                      (rabbits)                                      LOAEL is 25 mg/kg, based on
                                                                                      decreased bodyweights,
                                                                                      body weight gains, and
                                                                                      food consumption
                                                                                     Developmental
                                                                                     NOAEL is >= 25 mg/kg/day
                                                                                     LOAEL is not established
-------------------------------------------------------------------------------------
870.3800                             Reproduction and        0, 50, 300, or 1,800    Parental
                                      fertility effects       ppm(0/0, 3.7/4.4,      NOAEL is 50 ppm (equivalent
                                      (rats)                  22.3/26.5, and132.9/    to 3.7/4.4mg/kg/day [M/F]
                                                              153.4 mg/kg bw/day [M/ LOAEL is 300 ppm
                                                              F]                      (equivalent to 22.3/26.5mg/
                                                                                      kg/day [M/F] based on
                                                                                      increased relativekidney
                                                                                      weight and hyaline droplet
                                                                                      depositionin the proximal
                                                                                      tubules of the kidneys in
                                                                                      themales and increased
                                                                                      blood serum LH levels
                                                                                      inthe F1 females
                                                                                     Offspring
                                                                                     NOAEL is 300 ppm
                                                                                      (equivalent to 22.3/26.5mg/
                                                                                      kg/day [M/F]. LOAEL is
                                                                                      1,800 ppm(equivalent to
                                                                                      132.9/153.4 mg/kg/day [M/
                                                                                      F]based on decreased
                                                                                      absolute and relative
                                                                                      tobody uterus weights and
                                                                                      delayed sexualmaturation
                                                                                      in the F1 females
                                                                                     Reproductive Performance
                                                                                     NOAEL is 1,800 ppm
                                                                                      (equivalent to 132.9/
                                                                                      153.4mg/kg/day [M/F]
                                                                                     LOAEL for reproductive
                                                                                      performance was
                                                                                      notobserved
-------------------------------------------------------------------------------------
870.4100                             Chronic toxicity        0, 3, 8, or 20 mg/kg/   NOAEL is 8 mg/kg/day
                                      (dogs)                  day                    LOAEL is 20 mg/kg/day,
                                                                                      based on acute clinical
                                                                                      signs(vomiting, mostly
                                                                                      within the first week),
                                                                                      clinical pathology at 12
                                                                                      months (higher
                                                                                      reticulocytes counts) in
                                                                                      males and females
-------------------------------------------------------------------------------------
870.4200                             Carcinogenicity (mice)  0, 250, 750, or 2250    NOAEL was not established
                                                              ppm(0/0, 29/38, 88/    LOAEL is 250 ppm
                                                              112, or261/334 mg/kg/   (equivalent to 29/38mg/kg/
                                                              day [M/F]               day [M/F]), based on
                                                                                      minimal tomoderate
                                                                                      centrilobular
                                                                                      hepatocellularhypertrophy,
                                                                                      minimal to
                                                                                      severeextramedullary
                                                                                      hematopoiesis, minimal
                                                                                      tomoderate pigment
                                                                                      deposition in the
                                                                                      sternalbone marrow, and
                                                                                      increased incidence of
                                                                                      tissuemasses/nodules in
                                                                                      the lungs in the males,
                                                                                      andminimal to moderate
                                                                                      decreased cellularity
                                                                                      inthe femoral bone marrow
                                                                                      andhyperplasia/hypertrophy
                                                                                      of the epithelial cellsof
                                                                                      the terminal bronchioles
                                                                                      of the females
                                                                                     At the doses tested, the
                                                                                      carcinogenic potentialof
                                                                                      IKI-220 (flonicamid) is
                                                                                      positive at 250 ppmin
                                                                                      males and females based on
                                                                                      the increasedincidence of
                                                                                      alveolar/bronchiolar
                                                                                      adenomas,carcinomas, and
                                                                                      combinedadenomas/
                                                                                      carcinomas. Dosing was
                                                                                      consideredadequate based
                                                                                      on increased incidence of
                                                                                      tissuemasses/nodules in
                                                                                      the lungs and
                                                                                      microscopicfindings in the
                                                                                      liver, spleen, bone
                                                                                      marrow, andlungs. However,
                                                                                      data were
                                                                                      providedsuggesting this
                                                                                      effect is specific to
                                                                                      sensitivestrains of mice
                                                                                     Carcinogenic in mice
-------------------------------------------------------------------------------------

[[Page 51608]]

 
870.4200                             Carcinogenicity (mice)  0, 10, 25, 80, 250      NOAEL is 80 ppm (equivalent
                                                              ppmmales: 0, 1.20,      to 10/12mg/kg/day in males/
                                                              3.14, 10.0,30.3 mg/kg/  females)
                                                              day; females: 0,1.42,  LOAEL is 250 ppm
                                                              3.67, 11.8, 36.3 mg/    (equivalent to 30/36mg/kg/
                                                              kg/day                  day in males/females)
                                                                                      based on lungmasses and
                                                                                      terminal bronchiole
                                                                                      epithelial cellhyperplasia/
                                                                                      hypertrophy in both sexes
                                                                                     At the doses tested, the
                                                                                      carcinogenic potentialof
                                                                                      IKI-220 (flonicamid) is
                                                                                      positive in males
                                                                                      andfemales based on the
                                                                                      incidences ofalveolar/
                                                                                      bronchiolar adenomas,
                                                                                      carcinomas,and combined
                                                                                      adenomas and/or
                                                                                      carcinomas. Dosing was
                                                                                      consideredadequate based
                                                                                      on lung masses and
                                                                                      terminal bronchiole
                                                                                      epithelialcell hyperplasia/
                                                                                      hypertrophy in both sexes
                                                                                     Carcinogenic in mice
-------------------------------------------------------------------------------------
870.4300                             Combined Chronic/       0, 50 (males), 100      NOAEL is 200 ppm
                                      carcinogenicity         (males),200, 1,000,     (equivalent to 7.32/8.92mg/
                                      (rats)                  or 5,000 (females)      kg/day in males/females)
                                                              ppm (0/0, 1.84,3.68,   LOAEL is 1,000 ppm
                                                              7.32/8.92, 36.5/44.1,   (equivalent to 36.5/44.1mg/
                                                              and 219 mg/kg/day [M/   kg/day in males/females)
                                                              F]                      based ondecreased body
                                                                                      weights and body weight
                                                                                      gains,and increased
                                                                                      incidences of keratitis in
                                                                                      malesand striated muscle
                                                                                      fiber atrophy in females
                                                                                     At the high dose there was
                                                                                      an incidence (12%)of
                                                                                      nasolacrimal duct squamous
                                                                                      cell carcinomasslightly
                                                                                      outside the historical
                                                                                      control range (0-10%) in
                                                                                      male rats. A correlation
                                                                                      between theincidence of
                                                                                      inflammation and the
                                                                                      fluctuatingincidence of
                                                                                      nasal tumors was made
                                                                                      acrossdose groups. EPA did
                                                                                      not consider
                                                                                      thenasolacrimal duct
                                                                                      tumors to be treatment-
                                                                                      related
                                                                                     Female rats had a
                                                                                      significant increasing
                                                                                      trendin nasolacrimal duct
                                                                                      squamous cell carcinomasat
                                                                                      <0.05, and at the high
                                                                                      dose was slightlyabove the
                                                                                      historical control mean
                                                                                      (0.8%) andrange (0-4%).
                                                                                      EPA considered the
                                                                                      nasolacrimal duct
                                                                                      squamouscell carcinomas to
                                                                                      be possibly treatment
                                                                                      related, but that a
                                                                                      clearassociation with
                                                                                      treatment could not be
                                                                                      made
-------------------------------------------------------------------------------------
870.5100                             Bacterial reverse       61.7 to 5,000 [mu]g/    Negative
                                      mutation                plate +/-S9
-------------------------------------------------------------------------------------
870.5100                             Bacterial system,       33 to 5,000 [mu]g/      Negative for metabolite
                                      mammalian               plate +/- S9            TFNA
                                      activationgene
                                      mutation
-------------------------------------------------------------------------------------
870.5100                             Bacterial system,       33 to 5,000 ug/plate +/ Negative for metabolite
                                      mammalian               - S9                    TFNA-AM
                                      activationgene
                                      mutation
-------------------------------------------------------------------------------------
870.5100                             Bacterial system,       33 to 5,000 ug/plate +/ Negative for metabolite
                                      mammalian               - S9                    TFNG-AM
                                      activationgene
                                      mutation
-------------------------------------------------------------------------------------
870.5100                             Bacterial system,       33 to 5,000 [mu]g/      Negative for metabolite
                                      mammalian               plate +/- S9            TFNA-OH
                                      activationgene
                                      mutation
-------------------------------------------------------------------------------------
870.5100                             Bacterial               5 to 5000 ug/plate +/-  Negative for metabolite
                                      system,mammalian        S9                      TFNG
                                      activation gene
                                      mutation
-------------------------------------------------------------------------------------

[[Page 51609]]

 
870.5300                             In vitro mammalian      28.3 to 2,290 [mu]g/mL  Negative
                                      cellgene mutation       initialtest, and 143
                                                              to 2,290[mu]g/mL
                                                              repeat
-------------------------------------------------------------------------------------
870.5375                             In vitro Cytogenetics   573, 1145 and 2290      Negative
                                                              [mu]g/mL
-------------------------------------------------------------------------------------
870.5395                             In vivo                 Twice orally by         Negative
                                      cytogenetic(micronucl   intragastricgavage at
                                      eus) test in mice       doses of 250, 500and
                                                              1,000 mg/kg/day
                                                              formales and 125, 250
                                                              and 500mg/kg/day for
                                                              females
-------------------------------------------------------------------------------------
Non-guideline                        Other genotoxicity, in  Single doses of 375,    Was not positive for
                                      vivo Comet assay        750 and 1,500 mg/kg     nuclear migration up
                                                                                      to1,500 mg/kg
-------------------------------------------------------------------------------------
Non-guideline                        Unscheduled DNA         Once orally at 600 and  Is not genotoxic in
                                      synthesis               2,000 mg/kg             hepatocytes from treated
                                                                                      rats
-------------------------------------------------------------------------------------
870.6200                             Acute                   0, 100, 300, 600        NOAEL is 600 mg/kg in males
                                      neurotoxicityscreenin   (males), or 1,000 mg/   and 300 mg/kgin females
                                      g battery (rats)        kg/day                 LOAEL is 1,000 mg/kg based
                                                                                      on mortality andsigns of
                                                                                      toxicity (decreased motor
                                                                                      activity,tremors, impaired
                                                                                      respiration, and
                                                                                      impairedgait) in males
                                                                                     This acute neurotoxicity
                                                                                      study is
                                                                                      unacceptablebecause
                                                                                      interval motor activity
                                                                                      data were notprovided as
                                                                                      specified according to
                                                                                      guidelines,FOB handling
                                                                                      and open-field
                                                                                      observationswere
                                                                                      incomplete, and positive
                                                                                      data providedwere from a
                                                                                      lab other than the
                                                                                      performing labfor this
                                                                                      study. This study is not
                                                                                      required forthis risk
                                                                                      assessment and additional
                                                                                      informationis not required
-------------------------------------------------------------------------------------
870.6200                             Subchronic              0, 200, 1000, or        NOAEL is 200/1,000 ppm
                                      neurotoxicity           10,000 ppm(0/0, 13/     (equivalent to 13/81mg/kg/
                                      screeningbattery        16, 67/81, or625/722    day [M/F]
                                      (rats)                  mg/kg/day [M/F]        LOAEL is 1,000/10,000 ppm
                                                                                      (equivalent to67/722 mg/kg/
                                                                                      day [M/F] based on
                                                                                      decreasedmotor activity,
                                                                                      rearing, and foot splay
                                                                                      inmales, decreased body
                                                                                      weights, body weightgains,
                                                                                      and food consumption in
                                                                                      males andfemales
-------------------------------------------------------------------------------------
870.7485                             Metabolism              Pilot excretion study,  IKI-220 (flonicamid) was
                                      andpharmacokinetics     singleoral dose 0.85    rapidly absorbed
                                      (rats)                  or 21 mg/kgand pilot    andexcreted with no
                                                              pharmacokineticstudy,   apparent differences
                                                              single oral dose of     betweenthe sexes. By 48
                                                              2or 50 mg/kg            hours after treatment,
                                                                                      93%of the administered
                                                                                      dose had been
                                                                                      eliminatedand by 168 hours
                                                                                      ~96% was eliminated.
                                                                                      Theprimary route of
                                                                                      elimination was the
                                                                                      urine,accounting for ~90%
                                                                                      of the dose. The feces
                                                                                      oftreated rats accounted
                                                                                      for ~5% of theadministered
                                                                                      dose, with no significant
                                                                                      amountsof radiolabel
                                                                                      detected in expired air of
                                                                                      eithersex. After 168 hours
                                                                                      of a single high or
                                                                                      lowdose of the test
                                                                                      material, <3% of
                                                                                      theradioactivity was
                                                                                      recovered in the carcass
                                                                                      and<0.05% in the blood,
                                                                                      irrespective of dose orsex
                                                                                     The pharmacokinetic
                                                                                      parameters were
                                                                                      alsosimilar between the
                                                                                      dose levels (2 and 50mg/
                                                                                      kg) and sexes. The
                                                                                      radiolabel was
                                                                                      rapidlyabsorbed and
                                                                                      excreted. The apparent
                                                                                      plasmahalf-life
                                                                                      (T[frac1s2]) was 4.8-6.0
                                                                                      hours and theelimination
                                                                                      followed first order
                                                                                      kinetics. Thetime of
                                                                                      maximum plasma
                                                                                      concentration(Tmax) for
                                                                                      individual animals ranged
                                                                                      from0.25 to 1 hour after
                                                                                      treatment (with a mean
                                                                                      foreach group of 0.3-0.6
                                                                                      hours)
-------------------------------------------------------------------------------------

[[Page 51610]]

 
870.7485                             Metabolism and          2 or 400 mg/kg          Appears that the overall
                                      pharmacokinetics                                recovery ofradioactive
                                      (rats)                                          dose from all group was 94-
                                                                                      99% by168 hours post-dose.
                                                                                      Absorption was rapidand
                                                                                      extensive, detected in
                                                                                      plasma within 10minutes of
                                                                                      dosing, with maximum
                                                                                      plasmaconcentrations
                                                                                      within 24-54 minutes. By
                                                                                      168hours post-dose, total
                                                                                      urinary excretion was72-
                                                                                      78%, cage rinse was 10-
                                                                                      21%, and fecalexcretion
                                                                                      was 4-7% dose. Parent (IKI-
                                                                                      220)(flonicamid) and 9
                                                                                      metabolites accounted
                                                                                      for80-94% of the dose for
                                                                                      all groups. Parent
                                                                                      wasdetected primarily in
                                                                                      the urine, 46-73% of
                                                                                      thedose in excreta in all
                                                                                      groups. The
                                                                                      primarymetabolite was 4-
                                                                                      trifluoromethylnicotinamid
                                                                                      e(TFNA-AM), 18-27% dose in
                                                                                      all dose groups,along with
                                                                                      minor amounts of TFNA-AM N-
                                                                                      oxide (1-4% dose).Other
                                                                                      metabolites in urine and
                                                                                      feces were detected atless
                                                                                      than or equal to 2.5% of
                                                                                      the dose.IKI-220
                                                                                      (flonicamid) was excreted
                                                                                      primarily unchangedin the
                                                                                      urine, but
                                                                                      biotransformation of IKI-
                                                                                      220(flonicamid) in rats
                                                                                      included nitrile
                                                                                      hydrolysis,N-oxidation,
                                                                                      hydroxylation of the
                                                                                      pyridine ring and
                                                                                      amidehydrolysis
----------------------------------------------------------------------------------------------------------------

B. Toxicological Endpoints

    For hazards that have a threshold below which there is no 
appreciable risk, the dose at which no adverse effects are observed 
(the NOAEL) from the toxicology study identified as appropriate for use 
in risk assessment is used to estimate the toxicological level of 
concern (LOC). However, the lowest dose at which adverse effects of 
concern are identified (the LOAEL) is sometimes used for risk 
assessment if no NOAEL was achieved in the toxicology study selected. 
An uncertainty factor (UF) is applied to reflect uncertainties inherent 
in the extrapolation from laboratory animal data to humans and in the 
variations in sensitivity among members of the human population as well 
as other unknowns. An UF of 100 is routinely used, 10X to account for 
interspecies differences and 10X for intraspecies differences.
    Three other types of safety or uncertainty factors may be used: 
``Traditional uncertainty factors;'' the ``special FQPA safety 
factor;'' and the ``default FQPA safety factor'' By the term 
``traditional uncertainty factor,'' EPA is referring to those 
additional factors used prior to FQPA passage to account for database 
deficiencies. These traditional uncertainty factors have been 
incorporated by the FQPA into the additional safety factor for the 
protection of infants and children. The term ``Special FQPA safety 
factor refers to those safety factors that are deemed necessary for the 
protection of infants and children, primarily as a result of the 
FQPA.'' The ``default FQPA safety factor'' is the additional 10X safety 
factor that is mandated by the statute unless it is decided that there 
are reliable data to choose a different additional factor (potentially 
a traditional uncertainty factor or a special FQPA safety factor).
    For dietary risk assessment (other than cancer) the Agency uses the 
UF to calculate an acute or chronic reference dose (acute RfD or 
chronic RfD) where the RfD is equal to the NOAEL divided by an UF of 
100 to account for interspecies and intraspecies differences and any 
traditional uncertainty factors deemed appropriate (RfD = NOAEL/UF). 
Where a special FQPA safety factor or the default FQPA safety factor is 
used, this additional safety factor is applied to the RfD by dividing 
the RfD by such additional factor. The acute or chronic Population 
Adjusted Dose (aPAD or cPAD) is a modification of the RfD to 
accommodate this type of safety factor.
    For non-dietary risk assessments (other than cancer) the UF is used 
to determine the LOC. For example, when 100 is the appropriate UF (10X 
to account for interspecies differences, and 10X for intraspecies 
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to 
exposure (margin of exposure (MOE) = NOAEL/exposure) is calculated and 
compared to the LOC.
    A summary of the toxicological dose and endpoints for flonicamid 
used for human risk assessment is shown in Table 2 of this unit:

            Table 2.--Toxicological Doses and Endpoints for Flonicamid Human Health Risk Assessments
----------------------------------------------------------------------------------------------------------------
                                                              Special FQPA SF* and
         Exposure Scenario              Dose Used in Risk     Level of Concern for     Study and Toxicological
                                         Assessment, UF          Risk Assessment               Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary                        None                    FQPA SF = NA            Quantitative risk
                                                             aPAD = NA.............   assessment is notrequired
                                                                                      since there are no acute
                                                                                      dietarytoxicity concerns
-------------------------------------------------------------------------------------

[[Page 51611]]

 
Chronic dietary                      NOAEL = 3.7 mg/kg/day   FQPA SF = 1             2-Generation Reproduction
                                     UF = 100..............  aPAD = chronic RfD/      rat
                                     Chronic RfD = 0.04mg/    FQPA SF= 0.04 mg/kg/   Parental
                                      kg/day.                 day.                   LOAEL = 22 mg/kg/day
                                                                                      basedon increased kidney
                                                                                      weights, kidney hyaline
                                                                                      deposition, increased
                                                                                      blood serum LH (F1
                                                                                      females)
-------------------------------------------------------------------------------------
Cancer                                              Suggestive evidence of carcinogenic potential
----------------------------------------------------------------------------------------------------------------
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL =
  lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference
  dose, MOE = margin of exposure, LOC = level of concern, NA = Not Applicable

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Tolerances are being 
proposed for the combined residues of flonicamid and its metabolites, 
in or on a variety of raw agricultural commodities. Risk assessments 
were conducted by EPA to assess dietary exposures from flonicamid and 
its metabolites in food as follows:
    i. Acute exposure. Quantitative acute dietary exposure and risk 
assessments are performed for a food-use pesticide, if a toxicological 
study has indicated the possibility of an effect of concern occurring 
as a result of a 1-day or single exposure. No such effects were 
identified in the toxicological s