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triflumizole (Terraguard, Procure) Pesticide Tolerance 5/02

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

Bureau of Pesticides Management
Pesticide Product Registration Section
625 Broadway, Albany, New York 12233-7257
Phone 518-402-8768     FAX 518-402-9024
Website: http://www.dec.state.ny.us/website/dshm/pesticid/pesticid.htm
E-Mail: ppr@gw.dec.state.ny.us

August 13, 2004

CERTIFIED MAIL
RETURN RECEIPT REQUESTED


Ms. Theresa K. Haas
State Registration Coordinator
Crop Protection
Research & Development
Crompton Corporation
74 Amity Road
Bethany, Connecticut 06524-3402

Dear Ms. Haas:

Re: Denial of Application for Registration of Revised Labels for Procure 50WS (EPA Reg. No. 400-431) and Terraguard 50W (EPA Reg. No. 400-433), and Denial of Application for Registration of One New Product Terraguard LS (EPA Reg. No. 400-502) Which Represent Major Changes in Labeling for the Active Ingredient Triflumizole

    The New York State Department of Environmental Conservation (Department) has reviewed your application, received January 16, 2004, to register revised labels for Procure 50WS (EPA Reg. No. 400-431) and Terraguard 50W (EPA Reg. No. 400-433), and to register the new product Terraguard LS (EPA Reg. No. 400-502) in New York State. The new labels represent major changes in labeling for the active ingredient triflumizole (chemical code 128879).

    Procure 50WS (EPA Reg. No. 400-431) is currently labeled as a broad-spectrum foliar fungicide for control of certain diseases of grapes and pome fruits (apples and pears) at a maximum application rate of one lb. ai/acre/season (grapes) and two lbs. ai/acre/season (pome fruits). The revised label adds use on cucurbits (1.25 lbs. ai/acre/season), cherries (3.0 lbs. ai/acre/season) and strawberries (1.0 lb. ai/acre/season).

    Terraguard 50W (EPA Reg. No. 400-433) is currently labeled as an ornamental fungicide which can be used in repeat applications as a cutting soak, soil drench, foliar spray or through chemigation for control of certain diseases on ornamental plants grown in enclosed commercial structures such as greenhouses, shadehouses, nurseries and interiorscapes. The revised label adds outdoor use on nurseries, including Christmas tree/conifer plantations.

    Terraguard LS (EPA Reg. No. 400-502) is labeled as a foliar spray only to landscape grown ornamental trees, shrubs, apples, pears and grapes in landscaped areas around residences; institutions; public, commercial and industrial buildings; recreational sites, such as campgrounds, golf courses, parks and athletic fields; rights of way and other easements. The maximum application rate on ornamentals, trees, and shrubs is 3.0 lbs. ai/acre/season.

    The application was deemed complete for purposes of review on March 16, 2004 and a registration decision is due by August 23, 2004.

    The Department has reviewed the information supplied to date in support of registration of the revised labels for Procure 50WS (EPA Reg. No. 400-431) and Terraguard 50W (EPA Reg. No. 400-433), and registration of the new product Terraguard LS (EPA Reg. No. 400-502).

    The New York State Department of Health (DOH) stated that neither triflumizole nor the three formulated products, Procure SOWS, Terraguard 50W and Terraguard LS, which are virtually identical in formulation, were very toxic in acute oral, dermal and inhalation toxicity studies. In dermal irritation studies (tested on rabbits), neither the active ingredient nor the formulated products were irritating to the skin. In eye irritation studies the active ingredient was slightly irritating to the eyes (tested on rabbits), whereas the formulated products were moderately irritating. The active ingredient as well as the formulated products were skin sensitizers (tested on guinea pigs).

    Triflumizole caused some toxicity in chronic animal feeding studies. In a chronic feeding/oncogenicity study in rats, triflumizole caused adverse liver effects (eosinophilic foci in males, and fatty vacuolation and inflammation and necrosis in females) at the lowest doses tested, which were 3.5 milligrams per kilogram body weight per day (mg/kg/day) in male rats and 4.5 mg/kg/day in females. In mice, liver lesions were observed at 67.4 and 86.1 mg/kg/day for males and females, respectively. The respective no-observed-effect levels (NOELS) were 16.2 and 21.7 mg/kg/day. In' dogs, an increase in liver weights and alkaline phosphatase activity were reported for males at a dose of 34.1 mg/kg/day and for females at 35.2 mg/kg/day. The respective NOELS were 10.0 mg/kg/day and 10.7 mg/kg/day.

    Triflumizole caused some developmental toxicity in the offspring of rats and rabbits. In a rat oral developmental toxicity study, a decrease in the number of viable fetuses and an increase in the incidence of cervical ribs were observed at 35 mg/kg/day; the NOEL was 10 mg/kg/day.

    In this study, maternal toxicity which was characterized by a decrease in body weight gain and food consumption and an increase in spleen and liver weights, was reported at a dose level of 35 mg/kg/day with a NOEL of 10 mg/kg/day. In a rabbit oral developmental toxicity study, adverse effects characterized by an increase in fetal and litter incidences of lumbar ribs, which is a skeletal variation, were observed at a dose of 100 mg/kg/day; the reported NOEL was 50 mg/kg/day. Maternal toxicity (decrease in body weight gains and food consumption) occurred at 100 mg/kg/day with a NOEL of 50 mg/kg/day. In a multi-generation reproduction study in rats, triflumizole caused an increase in gestation length in the third generation at 3.5 mg/kg/day; the NOEL was 1.5 mg/kg/day. In this same study, a decrease in pup weight and litter size was reported at a dose of 8.5 mg/kg/day; the observed NOEL was 3.5 mg/kg/day. No parental toxicity was observed at the highest dose tested, which was 8.5 mg/kg/day. The United States Environmental Protection Agency (USEPA) Office of Pesticide Programs (OPP) established a reference dose (RID) of 0.005 mg/kg/day based on the NOEL of 1.5 mg/kg/day in the multi-generation reproduction study in rats and an uncertainty factor of 300. This RfD has not yet been adopted by the USEPA's Integrated Risk Information System (IRIS).

    Triflumizole did not cause oncogenic effects in either rat or mouse chronic feeding studies. It also was negative in a number of genotoxicity studies. The USEPA classified triflumizole as a "Group E" chemical: evidence for noncarcinogenicity for humans.

    The USEPA established tolerances for triflumizole residues in or on cucurbits at 0.5 parts per million (ppm); strawberries (2.0 ppm) and cherries (1.5 ppm). The chronic population adjusted dose (cPAD) for triflumizole is 0.005 mg/kg/day and has the same basis as the RfD. The U.S. EPA estimated that chronic dietary exposure to triflumizole residues would be eight percent of the cPAD for the general U.S. population, eleven percent for all infants less than one year old and 18 percent for children one to six years old. This chronic exposure analysis is based on the conservative assumption that for most crops including cucurbits, strawberries and cherries, 100 percent of the crop would be treated with triflumizole. Also used in estimating these exposures were anticipated residues and average weighted percent crop treatment information for certain crops.

    The USEPA conducted a risk assessment for dermal and inhalation exposure of workers to triflumizole from its use on cucurbits, cherries, strawberries and ornamentals. For mixers/loaders/applicators, the combined margins of exposure (MOEs) for dermal and inhalation exposures were estimated to range from about 1,000 to 175,000. For these estimates, it was assumed that workers used personal protective equipment (PPE) as listed on the current pesticide product labels (long-sleeved shirt, long pants, waterproof chemical-resistant gloves and shoes plus socks). For dermal exposure, the USEPA used a dermal absorption factor of 3.5 percent and assumed 100 percent absorption for inhalation exposure. The NOEL used for estimating these MOEs was 8.5 mg/kg/day from a multi-generation reproduction study in which the toxicity endpoint was a decrease in body weight gain in rat pups during lactation. However, the USEPA classified this study as unacceptable and we believe that the NOEL for the same developmental endpoint from a second rat multi-generation reproduction study which the USEPA did find acceptable should be used in estimating the MOEs. If this NOEL of 3.5 mg/kg/day for decreased body weight gain in pups is used, then the estimated MOEs for combined dermal and inhalation exposures range from about 400 to 73,000. Generally, the USEPA considers MOEs of 100-fold or greater to provide adequate worker protection. For post-application occupational activities (e.g., irrigation, scouting, hand weeding), the estimated MOEs are about 230.

    There are no chemical specific federal or State drinking water/groundwater standards for triflumizole. Based on its chemical structure, this compound falls under the 50 microgram per liter New York State drinking water standard for "unspecified organic contaminants" (10 NYCRR Part 5, Public Water Systems). Based on the USEPA OPP RfD of 0.005 mg/kg/day and DEC Water Quality Regulation procedures for deriving surface water and groundwater standards and guidance values from non-oncogenic effects (6 NYCRR-Part 702.5), the ambient water quality value for triflumizole would be 35 micrograms per liter.

    The available information on triflumizole and the three formulated products, Procure 50WS, Terraguard 50W and Terraguard LS, indicates that overall the active ingredient and these formulated products are not very acutely toxic in laboratory animal studies. Although data from chronic and developmental/reproductive studies on triflumizole showed that this chemical has the potential to cause some toxicity, the expected exposure from the labeled uses of these three triflumizole-containing pesticide products should not pose a significant risk to workers or the general public. However, the skin sensitization and eye irritation studies in laboratory animals indicate that these three products can cause allergic skin reactions and moderate eye irritation. Skin sensitization concerns are mitigated by the product label's requirement to use chemical-resistant gloves made of waterproof material plus the wearing of a long-sleeved shirt and long pants. In addition, the labels precautionary statements state that prolonged or frequently repeated skin contact with the product may cause allergic skin reactions in some individuals. Although the precautionary statements also warn that these products cause moderate eye irritation, they do not require protective eyewear. The DOH recommends that the labels be revised to include this requirement, which appears consistent with the guidelines in the August 2003, USEPA Label Review Manual for such products. The labeled use of Procure 50WS, Terraguard 50W and Terraguard LS do not seem to pose significant risks to workers or the general public, and the DOH does not object to the registration of these products in New York State, provided that the above recommended product label change is made by the registrant.

    The Department's groundwater staff stated that the studies for triflumizole were performed back in the 1980's. The information presented in the original Data Evaluation Record reports (DERs) conflict with the information presented in the June 17, 1993 Environmental Fate and Ground Water Branch (EFGWB) memorandum. Therefore, information from the more recent memorandum is being presented.

Technical Review

Solubility: The solubility of triflumizole is 129 mg/L.

Hydrolysis: Triflumizole had a half-life of 3.9 days at pH 5, 64.6 days at pH 7, and 8.9 days at pH 9.

Soil Photolysis: Triflumizole had a half-life of 32-64 hours.

Aqueous and Soil Photolysis: Triflumizole had a half-life of 2-4 days.

Aerobic Soil Metabolism: Triflumizole had a half-life of 18 days in an Oxford sandy loam with a pH of 5.6 and 7.34% OM.

Adsorption/Desorption: Mobility appears to be inversely related to organic matter content. Triflumizole has been found to be mobile in sands with organic matter content of < 1 %. According to the DER, the study was not acceptable because the soils were autoclaved prior to the study which may have affected their adsorptive properties. KocS were 289 in sand and 4113 in a silt loam.

Field Dissipation: New field dissipation study results were submitted with this application. In a non-upgradable study in North Carolina, the agency calculated half-life using all data (replicates) was 133 days in a sandy loam soil with 1.9% OM, a pH of 5.8 and an application rate of 2lbs (8 apps at .251b). The study was not acceptable because the parent and the degradates were not analyzed separately throughout the study.

In a non-upgradable study in California, the agency calculated half-life using all data (replicates) was 102 days in a sandy loam soil with 1.0% OM, a pH of 8.6 and an application rate of 2lbs (8 apps at .25 lb). The study was not acceptable because the parent and the degradates were not analyzed separately throughout the study.

EPA Comments: In the Environmental Fate and Effects Division (EFED) memorandum dated May 21, 2001, the USEPA stated:
Triflumizole is not likely to be persistent under most environmental conditions, and, except for soils in a sand textural class with low organic materials, unlikely to be very mobile. Laboratory findings are in agreement with field dissipation studies with regard to soil metabolism half-life (18 days) where triflumizole was specifically followed and abiotic degradation rates at similar environmental conditions (pH and photoperiod) in the laboratory. The relatively high Koc values in non-sand soils and the moderate adsorption characteristics in sandy soils with organic carbon content greater than one percent suggest that it has low potential to reach groundwater. Triflumizole will reach surface water in both the dissolved form and sorbed onto soils and the organic material for several weeks following application.
Computer Modeling: Running the model with Riverhead soil, an application rate of 3.0 lb ai/a/yr, a half-life of 133 days and a Koc of 289, the model predicted breakthrough at 1 year and cyclical peaks between 1.4 and 4.1. Modeling 1 lb ai/a/yr, the model predicted breakthrough at 1 year and cyclical peaks between 0.4 and 1.4 ppb.

Summary: The new information presented in the field dissipation study indicates that the half-life is much longer (102 and 133 days) than that described in the old aerobic metabolism study (18 days). This significant increase in half-life has caused the model to project an impact to groundwater of between 0.4 and 4.1 ppb, based on the 1 to 3 lb application rate for Procure 50WS and Terraguard LS. For Terraguard 50W, the application rate could be significantly higher for the drench method.

    Given this projection and the lack of groundwater data, the Department's groundwater staff objects to the registration of any label revisions which add outdoor use sites and/or increase the label rates. Staff also objects to the registration of any new products labeled for outdoor use until the company has provided documentation that this active ingredient does not significantly impact groundwater when used according to labeled rates.

    Therefore, based on the above-mentioned information, the Department hereby denies the application for registration of revised labels for Procure 50WS (EPA Reg. No. 400-431) and Terraguard 50W (EPA Reg. No. 400-433), and denies the application for registration of the new product Terraguard LS (EPA Reg. No. 400-502).

    You may pursue the options available under Article 33-0711 of the New York State Environmental Conservation Law.

    Procure 50WS (EPA Reg. No. 400-431) and Terraguard 50W (EPA Reg. No. 400-433) will continue to be registered in New York State only for the uses and application rates which are currently accepted by the Department. Procure 50WS is currently accepted for use on grapes and pome fruits (apples and pears) at a maximum application rate of one lb. ai/acre/season (grapes) and two lbs. ai/acre/season (pome fruits). Terraguard 50W is currently accepted for application as a cutting soak, soil drench, foliar spray or through chemigation on ornamental plants grown in enclosed commercial structures such as greenhouses, shadehouses, nurseries and interiorscapes.

    Only products bearing New York State accepted labeling are to be sold, offered for sale, distributed or used in New York State. Products are considered unregistered in New York State if they bear labeling which is not accepted in New York State. If unregistered products are found being sold, offered for sale, distributed or used in New York State, Crompton Corporation will be subject to enforcement actions by the Department.

    If Crompton Corporation can not guarantee that unregistered products will not be sold, offered for sale, distributed or used in New York State, then the Department suggests that the federal labels be modified to specify the accepted New York State uses and application rates.

    Please be reminded that the application fee is nonrefundable. If you wish to reapply, you must submit a new application for registration, applicable application fee and all required documents, including any additional groundwater information. Any available information or discussions regarding field dissipation and any updated or more current aerobic metabolism information should be submitted.

    The Department will not register any new products or accept revised labels for currently registered products which add outdoor use sites and/or increase the label rates until the Department's concerns regarding the potential for this active ingredient to significantly impact groundwater when used according to labeled rates are mitigated. If New York State registration is requested for Procure 50WS, Terraguard 50W, Terraguard LS or for any other product which contains triflumizole 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 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
R. Zimmerman/ R. Mungari - NYS Dept. of Ag. & Markets
W. Smith - Cornell University, PMEP