EPA 732-F-04-001 NEW CHEMICAL FACT SHEET 1. DESCRIPT ION OF THE CHEMICAL Generic Names: (CAS) N-(cyanomethyl)-4-(trifluoromethyI)-3-(pyridinecarboximide) or (UPAC) N-cyanomethyl-4-trifluoromethyl nicotinamide MolecuUr Formula: C9H6N3OF3 Molecule r Weight: 229.2 Structure: Common Name: Flonicamid Trade Nsme: Flonicamid, IKI-220 End Use Product Name: F1785 GH 50 WG EPA Shaughnessy Code (OPP Chemical Code): 128016 Chemica Abstracts Service (CAS) Number: 158062-67-0 Year of Initial Registration: 2003 Pesticide Type: Insecticide Producers: Technical Flonicamid - ISK Biosciences; End Use Product - FMC 2. USE PATTERNS AND FORMULATIONS Application S tes: Type and Methods of Application: Use on ornamental plants grown in commercial greenhouses and interiorscapes foliar spray Types of Formulations: 98.4% a.i. Technical; 50% wettable granular end-use product Target Pests: 3. SCIENCE FINDINGS Aphids, thrips, whiteflies, leafhoppers, mealybugs, plant bugs, scale, stinkbugs SUMMARY STATEMENT The toxicology data base is complete for this use pattern with one exception: a 90 day inhalation study is required as a condition of registration to address concerns for repeated exposure via the inhalation route as a result of greenhouse use. 1 ------- In a battery of acute toxicity studies Flonicamid technical is classified as Toxicity Category 111 fot oral exposure and Category IV for all other routes of exposure. It is not a dermal sensitizer. In a batiery of acute toxicity studies, F1785 GH 50 WG Insecticide is classified as Toxicity Category II for eye irritation, Category III for oral and dermal exposure, and Category IV for inhalation and dermal irritation. It is not a dermal sensitizer. For env ronmental fate and effects the submitted data are sufficient to support use in greenhouses ani interior landscapes. Based on the available data, the compound is readily susceptible to microbial degradation and is very mobile in the environment. Under certain conditions, flonicamid could move into surface and ground water through runoff and leaching. Wildlife, plants, drinking water, and ground water are not expected to be exposed to the pesticide for thti following reason: greenhouse applications differ from general agricultural uses in that runoff water from irrigation is not normally released directly back into the open environment. The Agency has determined that this use of flonicamid met the criteria for OP replacement. For this reason, the Agency has determined that registration of these products is in the public interest arid the products are eligible for registration under FIFRA Sec.3(c)(7)(C). CHEMICAL CHARACTERISTICS Tcchnica Grade Physical: Powder Color: Light Beige Odor: Odorless HUMAN HEALTH ASSESSMENT Acute Toxicity :>f Technical flonicamid Acute Oral - Rat: LD50(M) = 884 mg/kg; LD50(F) = 1768 mg/kg. Toxicity Category III Acute Dermal - Rat: I.DJ0(M) > 5000 mg/kg. Toxicity Category IV Acute Ii halation - Rat: LC50 > 4.9 mg/L Melting Point: Vapor Pressure: Henry's Law Constant: Qctanol-water partition coefficient (Kow): Water Solubility: Dissociation Constant in water: 157.5°C 9.43 x 10'7 Pa at 20°C 4.2 x 10-' PamVmole (20°C) 1.9 (30°) 5.3 g/L (20°C) Pka= 11.6 ±0.03 2 ------- Toxicity Category IV Primary Eye Irritation - Rabbit: Not an eye irritant Toxicity Category IV Primary Skin Irritation - Rabbit; Not a skin irritant. Toxicity Category IV Dermal Sensitization - Guinea Pig: Not a sensitizer.. Other toxicology data reviewed for this use are summarized in the following table: STUDY TYPE - DOSE LEVELS No Observed Adverse Effect Level (NOAEL) (mg/kg/day) Lowest Observed Adverse Effect Level (LOAEL) (mg/kg/day) DEVELOPMENTAL TOXICITY IN THE RAT 0, 20, 100, 500 nig/kg day Maternal - 100 Developmental - 100 Maternal - 500, increased liver weights, liver and kidney pathological changes, Dev elopmenial - 500, increased incidence of cervical ribs 13-WEEK FEEDING RAT 0,3, 12,60, 119 mg/ki/day (Mi 0, 15, 72, 340 mg/kg/< ay (F) 12 (M), 72 (F) 60 (M), 340 (F) • kidney hyaline deposition (M&Flt Production of blood cells in (issues other than bone marrow. This occurs in severe anemia and other diseases affecting the blood), liver ccmrilobular hypertrophy (F) 28-DAY RANGE-FINDING RAT 7 (Ml. 82 (F) 36 (M), 373 (F) - kidney hyaline deposition (M&F), liver cenlrilobular hypertrophy, anemia, and incr cholesterol (F ) 13-WEEK FEEDING DOG (capsules] 8 (M), 20(F) 20 (M), 50 (F) - clinical and hematology changes (M&F), increased adrenal weights & decreased thymus weights (M), kidney tubular vacuolation (F) 13-WEEK FEEDING MOUSE 15 (M), 20 (F) unacceptable study due to lack ofhistological examinations 154 (M). 192 (F) • clinical and hematology changes, spleen extramedullar hematopoiesis (Production of blood cells in tissues other than bone marrow This occurs in severe anemia and Qther diseases affecting the blood). 28-DAY DERMAL TOXICITY RAT 1000 >1000 METABOLISM - pilo pharmacokinetic and elimination study pilot study - unacceptable/ guideline - MUTAGENICITY negative - OCCUPATIONAL EXPOSURE The following er d points were identified for use in the occupational risk assessment for the greenhouse use: 3 ------- Summary of Toxicologieal Dose and Endpoints for Flonicamid (non-food use). Exposure Scenario Dose Used in Risk Assessment, UF Level of Concern for Risk Assessment Study and Toxicological Effects Long-Term Dermal (>6 months) Oral NOAEL= 12 mg/kg/day (dermal absorption rate = 3.6 %) Occupational LOC for MOE = 100 90-Day oral rat LOAEL = 60 mg/kg/day based on kidney hyaline deposition. Short- (1 to 30 days), Intermediate (1 to 6 months) and Long-Term (>6 months) Inhalation Oral NOAEL- 12 mg/kg/day (inhalation absorption rate = 100%) Occupational LOC for MOE = 100 90-Day oral rat LOAEL = 60 mg/kg/day based on kidney hyaline deposition. Cancer (oral, dermal, inhalaticn) Not determined. NA Studies not reviewed at this time. UF = uncertainty 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 In addition, the Agency evaluated the preliminary findings of male and female lung tumors in a flonicamid mouse oncogenicity study and determined an upper-bound Ql* of 0.0316 mg/kg/clay"1, which was used for a screening level cancer assessment for the proposed uses. A full evaluation of the study findings will be conducted in the event food-use petitions are submitted in th: future. Pesticide handl ;rs may be exposed to flonicamid during mixing, loading and application. Occupational pDstapplication exposure is expected for commercial greenhouse ornamental production and maintenance of interiorscapes. Postapplication activities for which exposure is anticipated include scouting, pinching, pruning, container relocation and re-planting (interiorscapes). Handler Exposure and Risk* Inhalation MOEs for non-cancer effects, at 5,200 to 520,000, are above the targe: of 100 without the use of a respirator. Therefore they are not of concern to the Agency. The h ighest estimated cancer risks for handlers (combined dermal and inhalation exposure) was (>.2 x 10 6 for a mixer/loader applicator. Characterization of Handler Exposure and Risk. The Agency believes that the use of maximum application rates to assess short-/intermediale-term exposure for flonicamid handlers leads to conservative exposure estimates. Handler risks were assessed separately from postapplication worker risks. This may underestimate or overestimate the risk to greenhouse workers who engage in both activities in a workday. However, the Agency believes that the 4 ------- uncertainties in attempting to assess a combined exposure, for which reliable data are lacking, would lead to an unreliable final risk estimate. Post Application Exposure and Risk. MOEs that exceed the target MOE of 100 are not of concern. The Agency estimated long-term dermal MOEs for post application exposure scenarios that exceeded 100. The most highly exposed worker is a hand pruner. where the long term dermal MOE is 700. C nicer risks range from 3.8 x lO" to 7,6x 10"5. For the hand pruner, the estimated cancer risk is 7.5 x 10 \ Characterization of Postapplication Exposure and Risk. For postapplication workers, a range of application n tes were assessed, including the maximum, central and lowest rate. Postapplication risks were estimated for long-term exposure, with the assumption that workers would be exposed > 180 consecutive days per year. A 4-hour per day exposure duration is used for estimating ciincer risk, and is considered to be a central-value assumption. However, the assumption of 2 DO annual working days of exposure to "day of treatment" residue levels, adds a conservative element to the results. The range of transfer coefficients used in this assessment is believed to be sufficient to cover most potential activities with greenhouse ornamentals and interiorscapes. The highest transfer coefficient used (7000 ug/cm2) is most relevant to cut flower harvesting and bundling, which only accounts fcr a subset of the activities subject to this application. Overall, the postapplication exposure assessment for flonicamid use on greenhouse ornamentals and interiorscapes is believed to result in high-end estimates of risk. Residential Exposure and Risk. There are no existing or proposed uses of flonicamid at residential sites. Currently, the Agency considers residential postapplication exposure to ornamental plan s to be negligible. Post application exposure includes incidental oral exposure to toddlers and exposure to ornamental plants in interiorscapes such as those found in public places such as shopping malls. ECOLOGICAL EFFECTS CHARACTERISTICS The Agency eva uated the studies submitted by the registrant and the results are presented below. In evaluating the submitted studies, the Agency considered the significance of EPA guideline deviations in the context of this particular application in greenhouses and interiorscapes and determined that deficient studies did not have to be repeated for greenhouse use. Avian dietary (Uobwhite quail). Flonicamid technical is categorized as slightly toxic to northern bobwhite quail on an acute dietary basis. The LCS0 is greater than 4613 mg/kg. The NOAEC (no observed adverse effect concentration) is less than 4613 mg/kg. The endpoint(s) affected were food consumption and body weight. 5 ------- Avian dietary (Mallard duck). Flonicamid technical is categorized as practically nontoxic to mallard ducks on an acute dietary basis. The LCJ0 is greater than 5037 nig/kg. The NO A EC is less than 5037 nig/kg. The endpoints affected were food consumption and body weight. Fish toxicity, warmwater species (bluegill sunfish). In a 96 hour acute toxicity study, flonicamid technical is categorized as slightly toxic to bluegill sunfish. The LC50 is greater than 98.8 mg a.i./L. "he NOAEC is greater than or equal to 98.8 mg a.i./L. No affected endpoints were identified n this study. Fish toxicity, coldwater species (rainbow trout). In a 96-hour acute toxicity study, flonicamid is categorized slightly toxic to rainbow trout. The LC50 is greater than 97.9 mg a.i./L. The NOAEC is grea.er than or equal to 97.9 mg a.i./L. No affected endpoints were identified in this study. Freshwater invertebrate toxicity (Daphnia magna). In a 48-hour acute toxicity study under static conditions, flonicamid is categorized as slightly toxic to freshwater invertebrates. The EC50 (concentration at which 50% of the test organisms were immobilized) is greater than 98.6 mg a.i./L. The NOAEC is greater than or equal to 98.6 mg a.i./L. Acute toxicity Green Alga- Tier 1. In a 72 hour acute toxicity study under static conditions, the NOAEC was 43.8 mg/L based on growth rate and biomass. Reductions in cell density, growth rate, and biomass did not exceed 50%, so the EC50 was greater than 96.7 mg/L. Honey bee - acute contact & oral LC^ Flonicamid is categorized as practically nontoxic to honeybees on both an acute contact and oral basis. ENVIRONMENTAL FATE The following table summarizes the environmental fate characteristics of flonicamid. See also the chemical characteristics summarized on page 2 of this fact sheet. PARAMETER value pH (20°C) 4.5 stable stable 204 days stable 77 days Hydrolysis half life pH 5) Hydrolysis half life pH 7) Hydrolysis half life pH 9) Aqueous photolysis half life Soil photolysis half life Soil-water distribution coefficient (Kd) 0.094 -0.454 mL/g CONTACT PE RSON: 6 ------- Ann Sibold, Reviewer, PM-10 Insecticide Brarch , Registration Division (7505C) Office of Pestic de Programs U.S. EPA, Ariel Rios Building 1200 Pennsylvania Avenue NW Washington, DC 20460 Office Location and Telephone Number: Rm. 220, Crystd Mall # 2 1921 Jefferson Davis Highway Arlington, VA 12202 (703) 305-6411 Electronic copies of the this fact sheet are available on the Internet. See http://www.epa.gov/opprd001/factsheets/ Printed copies of this fact sheet can be obtained from EPA's National Center for Environmental Publications and Information (EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-2419, telephone 1-800-490-9198; fax 513-489-8695. For more information about EPA's pesticide registration program, please contact the Registration Division (7505C), OPP, US EPA, Washington, DC 20460, telephone 703-305-5446. For infoimation about the health effects of pesticides, or for assistance in recognizing and managing pestic ide poisoning symptoms, please contact the National Pesticides Telecommunications Network (NPTN). Call toll-free 1-800-858-7378, from 6:30 a.m. to 4:30 p.m. Pacific Time, or 9:30 a.m. to 7:30 p.m. Eastern Standard Time, seven days a week. 7 ------- 4. TITLE AND SUBTITLE ft r i F fuor omctl iy f ?-3-^py r id N-cyanomethy -4-trif luoromelliy 1 nicorinamide 5. FUNDING NUMBERS 6. AUTHOR(S) EPA, Office of Pesticide Programs, Registration Division 7. PERFORMING ORG/NIZATlON NAMEJS) AND ADDRESS(ES) U.S. Environmental Protection Agency Office of Pesticide Programs Registration Division (7505C) 401 M Street, S.V. Washington, D.C. 20460 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAMEfS) AND ADDRESS(ES) Same as #7 10. SPONSORING /MONITORING AGENCY REPORT NUMBER EPA 732-F-04-001 11, SUPPLEMENTARY YOTES 12a. DISTRIBUTION/AVAILABILITY STATEMENT Publicly Available 12b. DISTRIBUTION CODE 13, ABSTRACT (Maximum 200 words) This document contains up-to-date chemical information, including a summary of the Agency's regulatory position and rationale, on a specific pesticide or group of pesticides. A Fact Sheet is issued after one of the following actions has occurred. 1. Issiance or reissuance of a registration standard, 2. Issi ance of each special review document, 3. Registration of a significantly changed use pattern, 4. Registration of a new chemical, or 5. An immediate need for information to resolve controversial issues relf.ting to a specific chemical or use pattern. 14. SUBJECT TERMS Pesticides; Regulation; Chemical Information Fact Sheet; Use Patterns , Science Findings 15. NUMBER OF PAGES 7 16. PRICE CODE 17. SECURITY CLASSIFICATION OF REPORT Unclassified IB. SECURITY CLASSIFICATION OF THIS PAGE , Unclassified 19. SECURITY CLASSIFICATION Un?LTsMId 20. LIMITATION OF ABSTRACT NbN 75*0-01 -2B0-5500 $*nn.d^'d -cm H93 (Rev 2-E9) ------- |