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Fenpyroximate (AkariTM 5SC) NYS DEC Letter - Registration of Active Ingredient 5/03

New York State Department of Environmental Conservation
Division of Solid and Hazardous Materials

Bureau of Pesticides Management, 9th Floor
625 Broadway Albany, New York 12233-7254
Phone: (518) 402-8788     FAX: (518) 402-9024
Website: www.dec.state.ny.us

May 27, 2003

CERTIFIED MAIL
RETURN RECEIPT REQUESTED


Ms. Marie A. Maks
Manager, Regulatory Affairs
Nichino America Incorporated
4550 New Linden Hill Road, Suite 501
Wilmington, Delaware 19808

Dear Ms. Maks:

Re: Registration of the New Active Ingredient Fenpyroximate, Contained in the Pesticide Product AkariTM 5SC Miticide/Insecticide (EPA Reg. No. 71711-4)

    The New York State Department of Environmental Conservation (Department) has reviewed your application, received December 11, 2002, to register the above-mentioned product in New York State. The product contains the new active ingredient fenpyroximate.

    The application was deemed complete for purposes of review on January 30, 2003 and a registration decision is due by June 27, 2003.

    AkariTM 5SC contains the new active ingredient fenpyroximate (tert-butyl (E)-alpha-(1,3-dimethyl-5-phenoxyprazol-4-ylmethylenaminoxy)-p-toluate). AkariTM 5SC is a contact miticide used for the control of spider mites on greenhouse ornamental, floral and foliage crops; indoor ornamental plantings and plantscapes. Fenpyroximate was granted reduced risk status on May 18, 1999 for the control of spider mites on indoor greenhouse ornamentals. For resistance management, this product is not to be used in successive miticide applications in the same greenhouse. At least two different chemicals with different modes of action are to be used between treatments with AkariTM 5SC. Resistance management strategies also recommend that application rates lower than recommended on the label are not to be used and for best results, no more than two applications of AkariTM 5SC per growing season, or per crop cycle (whichever is longer), be used.

    The Department has reviewed the information submitted to date in support of the application for registration of AkariTM 5SC Miticide/Insecticide (EPA Reg. No. 71711-4).

HEALTH EFFECTS:

    The active ingredient, fenpyroximate, was moderately toxic by the oral and inhalation routes of exposure and slightly toxic by the dermal route of exposure in acute toxicity laboratory animal studies. This active ingredient was not irritating to the skin or eyes (tested on rabbits). It was a slight to moderate skin sensitizer (tested on guinea pigs) by one test method, but was not sensitizing by another test method. The formulated product AkariTM 5SC Miticide/Insecticide was not very toxic in acute oral, dermal or inhalation exposure studies in laboratory animals. AkariTM 5SC Miticide/Insecticide was not a dermal irritant or sensitizer; however, it did cause moderate to severe, but reversible, eye irritation.

    Fenpyroximate caused some toxicity in subchronic animal feeding studies. In a 90-day rat feeding study, fenpyroximate caused decreased body weight gain at 6.6 milligrams per kilogram body weight per day (mg/kg/day); the no-observed-effect-level (NOEL) was 1.3 mg/kg/day. In a 90-day dog feeding study, fenpyroximate caused a slight decrease in heartbeat (bradycardia) and an increase in the incidence of diarrhea in both sexes at 2 mg/kg/day; a NOEL was not established in this study. Fenpyroximate at this dose level also caused reduced food consumption, body weight, and body weight gain, as well as emaciation and torpor in females. In a 21-day dermal toxicity study in rabbits, fenpyroximate caused reduced body weights, reduced body weight gain, and reduced food consumption in both sexes and an increase in absolute liver weights as well as a possible increase in hepatocellular necrosis in females at 1,000 mg/kg/day; the NOEL was 300 mg/kg/day.

    Fenpyroximate caused some toxicity in chronic animal feeding studies. In a one-year dog feeding study, fenpyroximate caused diarrhea, bradycardia, and decreases in cholesterol, body weight gain and food consumption in males, and vomiting, diarrhea, excessive salivation, and decreased cholesterol in females at a dose of 15 mg/kg/day; the NOEL was 5 mg/kg/day. In a chronic feeding/oncogenicity study in mice, decreased body weight gain and food consumption were reported at doses of 9.5 mg/kg/day for males and 10 mg/kg/day for females; the respective NOELS were 2.4 mg/kg/day and 2.5 mg/kg/day. In a chronic feeding/oncogenicity study in rats, decreased body weight was the only reported effect at 3.1 mg/kg/day in males and 3.8 mg/kg/day in females; the respective NOELs were 0.97 mg/kg/day and 1.2 mg/kg/day. The United States Environmental Protection Agency (USEPA), Office of Pesticide Programs established a reference dose (RfD) for fenpyroximate of 0.01 mg/kg/day based the NOEL of 0.97 mg/kg/day from this chronic rat feeding study and an uncertainty factor of 100 to account for interspecies extrapolation and human variability. This RfD has not yet been adopted by the USEPA's Integrated Risk Information System (IRIS).

    Fenpyroximate caused some developmental toxicity in offspring of laboratory animals at doses that also caused maternal toxicity. In a rat study, fenpyroximate caused an increase in the fetal incidence of additional thoracic ribs at 25 mg/kg/day; the NOEL was 5 mg/kg/day. Maternal toxicity, characterized by marginal depression in body weight and food consumption, occurred at 25 mg/kg/day; the NOEL was 5 mg/kg/day. In a rabbit study, no treatment-related effects were reported for maternal or developmental toxicity at doses up to 5 mg/kg/day, the highest dose tested. In a multi-generation reproduction study in rats, fenpyroximate caused decreased body weights during the pre-mating period at 6.6 mg/kg/day in males and 8.6 mg/kg/day in females; the NOELS were 2.0 mg/kg/day and 2.4 mg/kg/day, respectively. Reproductive toxicity was characterized by decreased lactational weight gain in both generations of pups at 8.6 mg/kg/day; the NOEL was 2.4 mg/kg/day.

    Fenpyroximate did not cause oncogenic effects in rat or mouse chronic feeding studies. This compound was also negative in a number of genotoxicity studies. The USEPA classified fenpyroximate as "not likely" to be carcinogenic to humans.

    The USEPA conducted an occupational risk assessment for dermal and inhalation exposures to fenpyroximate from use in an enclosed greenhouse. For determining margins of exposure (MOEs), the USEPA compared estimated short-term and intermediate-term dermal exposures to a NOEL of 300 mg/kg/day from the 21-day dermal toxicity study in rabbits. Short-term inhalation exposures were compared to a NOEL of 5 mg/kg/day from the developmental toxicity study in rats, and intermediate-term inhalation exposures were compared to a NOEL of 1.5 mg/kg/day (rather than a NOEL of 1.3 mg/kg/day as denoted earlier in our review) from the 90-day rat feeding study. For commercial mixer/loader/applicators, MOEs ranged between 1,200 for combined short-term dermal and inhalation exposures and 2,800 for intermediate-term dermal and inhalation exposures. These estimates assumed a maximum application rate of 0.34 pounds fenpyroximate per acre. It was also assumed that workers wore gloves, a long-sleeved shirt and pants as per label requirements. The MOE for post-application occupational exposure (cutting and harvesting of indoor ornamental plants) was estimated to be 490. Generally, the USEPA considers MOEs of 100-fold or greater to provide adequate worker protection.

    The available information indicates that fenpyroximate was slightly to moderately toxic in acute studies, but was not irritating to the eyes or skin. AkariTM 5SC Miticide/Insecticide was not very acutely toxic, but was a moderate to severe eye irritant. Fenpyroximate caused some effects in subchronic and chronic toxicity studies, and caused some developmental effects in the rat, but not the rabbit. Fenpyroximate was not oncogenic or genotoxic and was classified by the USEPA as "not likely" to be a human carcinogen. Greenhouse workers applying AkariTM 5SC Miticide/Insecticide and handling treated plants would be expected to have the greatest exposure to this pesticide product and its active ingredient fenpyroximate. However, the USEPA's occupational risk assessment determined that workers would have adequate MOEs. To mitigate the potential for eye injury from AkariTM 5SC Miticide/Insecticide, the product's label requires the use of protective eyewear. In addition, post-application impacts to air within greenhouses from use of AkariTM 5SC Miticide/Insecticide should not be a concern as fenpyroximate has a low vapor pressure (5.63 X 10-8 millimeters of mercury at 25 degrees Celsius) and the product does not contain volatile petroleum-based solvents. Finally, the USEPA determined that AkariTM 5SC could be an effective tool in resistance management and granted fenpyroximate reduced risk pesticide status for the labeled use.

ECOLOGICAL EFFECTS:

    AkariTM 5SC is 5% fenpyroximate, Tert-butyl(E)-alpha-(1,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneaminoxy)-p-toluate, a substituted pyrozole. Its mode of action is to interfere with mitochondrial electron transport. More specifically, it targets proton-translocating NADH:Q oxidoreductase and blocks ubiquinone reduction, similar to rotenone.

    Technical fenpyroximate water solubility is slightly pH dependant. Its solubility is 21.4, 23.1, and 29.8 parts per billion (ppb) at pHs 5, 7, and 9, respectively. It has low vapor pressure, 5.6 x 10-8 mmHg; volatilization will not contribute significantly to dissipation. Its octanol/water partition coefficient, Kow, is relatively high at 102,330 suggesting a potential to bioaccumulate. A Bluegill Sunfish accumulation study summary gives bioconcentration factors, BCF, of 656X, 2746X, and 1601X, for edible tissue, nonedible tissue, and whole fish respectively.

    Fenpyroximate is moderately toxic to mammals on an acute basis and is practically non-toxic to birds. The indoor greenhouse use pattern requires a much reduced set of aquatic organism toxicity tests. Those submitted show fenpyroximate to be very highly toxic to all organisms tested with LC50 values in the low 1 to 4 ppb range. No honeybee or aquatic plant study results were submitted.

    From the limited environmental fate data submitted it appears fenpyroximate may be relatively persistent and exhibit low post-application mobility. Its hydrolysis half-life, T,,2, is 226 days at pH 7 and aerobic soil T1/2s ranged from 35 to 161 days. Fenpyroximate photolyses readily, aqueous photolysis T1/2 equals 1.5 hours. In column leaching studies using three soils (sand, loamy sand, and sandy loam) parent fenpyroximate, 0.27% of that applied, was only detected in the leachate collected from the sand soil.

    No fish or wildlife exposure is anticipated from this use pattern. As such, no adverse effects to fish or wildlife resources are anticipated from labeled greenhouse use of AkariTM 5 SC.

    Nichino America, Inc. anticipates submitting an application in September 2003 for fenpyroximate use on apples and grapes in New York State. The majority of the requisite environmental fate and ecological effects study results will be submitted at that time.

ENVIRONMENTAL FATE:

    The maximum application rate of AkariTM 5SC is 0.68 lb ai/a/year as a foliar application, applied in two applications. The inerts do not appear to be solvent carriers.

    The Department's environmental fate staff stated the following:

    Hydrolysis: EPA found this study acceptable. Fenpyroximate had half-lives of 180, 226 and 221 days pHs 5, 7, and 9, respectively.

    Solubility: Fenpyroximate is soluble in water at a level of 0.023 mg/l at pH 7.

    Aqueous Photolysis: EPA found this study acceptable. Aqueous photolysis is a major degradative pathway. The half-life is very short at 1.5 hours. Two major degradates were found, M-1 [tert-butyl (Z)-a-(1,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneamino-oxy-p-toluate] and M-11 01,3-dimethyl-5-phenoxypyrazole-4-carbonitirile) were found at 59.8% and 22.2% respectively. M-1 then degraded with a half-life of 12.7 hours.

    Soil Photolysis: No studies were performed.

    Aerobic Soil Metabolism: Two aerobic soil metabolism studies were submitted (MRIDs # 44781017 and 44847910). Both studies were unacceptable and did not meet Subdivision N Guidelines for 162-1 for many reasons. On the first, the reviewer calculated half-lives were 159 days and 35 to 46.5 days. The registrant calculated half-lives were 16.9, 10.1, and 21.3 days in clay loam, silt loam and loam soils, respectively. In the second study, the reviewer calculated half-life was 161 days, and the registrant calculated half-life was 159 days.

    Adsorption/Desorption: One adsorption/desorption study was performed (MRID #44847911). The study was unacceptable and did not meet the Subdivision N Guidelines for 163-1 because the soils were autoclaved to sterilize them, and this is not an acceptable procedure. However, the adsorption Kocs of the soils were 40,000, 50,000, 40,000 and 44,000 for sand, sandy loam, clay loam and loam respectively. The desorption Kocs were 37,000, 44,000, 64,000 and 37,000 for sand, sandy loam, clay loam and loam respectively. Sterilization has been shown to alter the physical and chemical properties of the soil that affect the adsorption and desorption of chemicals. Since the Kocs range from 37,000 to 64,000, the Department believes the chemical would still be immobile, even with a significantly lower Koc. The Notice of Registration, dated September 27, 2000, indicated that this study had to be provided by September 27, 2003 [3 years].

    Aged Leaching: Three aged leaching studies were submitted (MRIDs # 44781018, 44781019, and 44781020). All three studies were unacceptable and did not meet Subdivision N Guidelines 163-1 for several reasons. No mobility data were presented in the summary. The Notice of Registration, dated September 27, 2000, indicated that this study had to be provided by September 27, 2003 [3 years].

    Terrestrial Field Dissipation: No studies were performed.

    EPA Comments: To support indoor use, generally the only environmental fate data required is a hydrolysis study. This study was submitted and found to be acceptable. A photolysis study was also submitted and found to be acceptable. There are no other acceptable environmental fate data for this chemical. Because this pesticide is very highly acutely toxic to fish and aquatic invertebrates, the following environmental fate data will be required, on a confirmatory basis, to provide a basic exposure profile for this pesticide: Guideline 162-1 Aerobic Soil Metabolism and Guideline 163-1 Adsorption/Desorption (Batch Equilibrium).

    There are no chemical specific federal or State drinking water/groundwater standards for fenpyroximate. Based on its chemical Structures, fenpyroximate falls under the 50 microgram per liter (/.cg/L) New York State drinking water standard for "unspecified organic contaminants" (10NYCRR Part 5, Public Water Systems).

    Given the very high Kocs, the foliar application, and the fact that this product is labeled for greenhouse use, the Department's environmental staff have no objection to the registration of this product as labeled. However, if the company wishes to add outdoor uses to the label, they should be prepared to submit the aerobic metabolism and leaching and adsorption studies and DERs at that time.

    AkariTM 5SC Miticide/Insecticide should not have an adverse effect on the health of workers or the general public, the fish and wildlife resources, or the ground and surface water of New York State when used as labeled.

    Therefore, the Department hereby accepts for general use registration in New York State AkariTM 5SC Miticide/Insecticide (EPA Reg. No. 71711-4) which contains the new active ingredient fenpyroximate.

    Enclosed are your Certificate of Registration and New York State stamped "ACCEPTED" label.

    Nichino America, Inc. is reminded that if New York State registration is requested for this product or for any other product which contains fenpyroximate with an increased application rate and/or expanded use sites, the product will be considered a Major Change in Labeling and the Department will require an extensive review.

    If you have any questions, please contact Mr. Samuel Jackling, Chief of our Pesticide Product Registration Section, at (518) 402-8768.

Sincerely,

Maureen P. Serafini
Director
Bureau of Pesticides Management

Enclosures
cc: w/enc. - N. Kim/D. Luttinger - NYS Dept. of Health
G. Good/W. Smith - Cornell University, PMEP
R. Zimmerman/R. Mungari - NYS Dept. of Ag and Markets