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Pyraclostrobin - NYS Registrations: Insignia, Headline, and Cabrio 12/04

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

December 22, 2004

CERTIFIED MAIL
RETURN RECEIPT REQUESTED


Ms. Judy Fersch
BASF Corporation
P.O. Box 13528
Research Triangle Park, North Carolina 27709-3528

Dear Ms. Fersch:

Re: Registration for Insignia (EPA Reg. No. 7969-184); Headline (EPA Reg. No. 7969-186); Cabrio EG Fungicide (EPA Reg. No. 7969-187); Containing the Active Ingredient Pyraclostrobin. Chemical Code #099100

    The New York State Department of Environmental Conservation (Department) has completed its technical review of your application for registration of Insignia (EPA Reg. No. 7969-184); Headline (EPA Reg. No. 7969-186); and Cabrio EG Fungicide (EPA Reg. No. 7969-187) and has registered these products for labeled use in New York State under condition that no product be applied via aerial application methods. Insignia, Headline, and Cabrio EG Fungicides contain the new active ingredient (NAI) pyraclostrobin ((carbamic acid, [2-[[[1-(4-chlorophenyl)-IH-pyrazol-3-yl]oxy]methylphenyl]methoxy-, methyl ester) which has not been registered previously in New York State.

    The Department received your application for the registration of the above-referenced products on May 5, 2004. The application was considered incomplete on June 28, 2004. BASF submitted additional United States Environmental Protection Agency (USEPA) Data Evaluation Records (DERs) which were received by this Department on July 7, 2004. The application was determined to be complete on August 18, 2004, in accordance with ECL §33-0704, a registration decision date of January 14, 2005 was established.

    Pyraclostrobin is a new broad spectrum foliar fungicide in the strobilurin chemical class. Cabrio, Headline, and Insignia are labeled for control of numerous fungal diseases on many different crops with use anticipated on virtually all major crops grown in New York State. BASF submitted a request on September 8, 2004 to add sites (crops) to the original review list pending federal approval. The Department granted BASF's request on condition that federally approved labeling be provided prior to registration of the additional use sites in New York State. The additional major changes in labeled use (sites) were incorporated into the new active ingredient technical review to limit review effort on behalf of the Department.

    Insignia fungicide contains 20% pyraclostrobin and is labeled for control or suppression of 19 fungal diseases in golf course turfgrass. Supplemental labeling was submitted by BASF on September 8, 2004, adding use on: residential, institutional, commercial and municipal lawns, parks, recreational areas, cemeteries, and sod farms. Applications of 22-40 oz/acre of Insignia or 0.275-0.51b active ingredient (ai)/acre are made at ten- to 28-day intervals using ground equipment only. A maximum of six applications or 3.0 lbs active ingredient may be made per season. The resistance management sequential application limit is two for four of the listed diseases and three for the remaining 13 diseases.

    Headline fungicide contains 23.6% pyraclostrobin and is labeled for control of fungal diseases in Citrus, Dry beans, Grass grown for seed, Peanuts, Sugar beets, Tuberous and Corm vegetables, Barley, Rye, and Wheat. Supplemental labeling was submitted by BASF on September 8, 2004, adding use on: Corn-field, sweet, and pop, Dried shelled Peas & beans subgroup, Edible podded legumes, Mint, Soybeans, Succulent shelled peas & beans, and Sunflowers. USEPA approved the supplemental labeling for the Cabrio EG Fungicide on November 30, 2004. Applications of six to 15 oz/acre of the Headline product or 0.1-0.25 lbs ai/acre, are made at seven- to 14-day intervals using ground, aerial (federally approved), or irrigation system equipment. The maximum number of applications allowed per season is two to six, depending on the crop, equaling 0.26-1.2 lbs ai/acre. To limit the potential for development of resistance, the number of sequential and total seasonal applications are limited. Only one application of Cabrio may be made in the presence of Downey mildew and Late blight, or any disease in cucurbits, before alternating to a fungicide with a different mode of action. Otherwise, two applications may be made before an alternate mode of action is used. The seasonal limits on the number of applications stated above are resistance management limits, as opposed to active ingredient poundage limits.

    Cabrio EG fungicide contains 20% pyraclostrobin and is labeled for control or suppression of fungal diseases on many New York grown crops within the following crop groups: Berries, Bulb, Cucurbit, Fruiting, and Root vegetables, and Cherries. Supplemental labeling was submitted by BASF on September 8, 2004, adding use on: Brassica-head, stem, and leafy greens, Leafy vegetables, Tuber vegetables, and Pomefruits. USEPA approved the supplemental labeling for the Cabrio EG Fungicide on December 1, 2004. Applications of eight to 16 ounces Cabrio product per acre or 0.1-0.2 lbs ai/acre, are made at seven- to 14-day intervals using ground, aerial (federally approved), or irrigation system equipment. The maximum number of applications per season range from three to six depending on the crop. Maximum seasonal application rates equal 0.6-1.2 lbs active ingredient per acre, also depending on the crop. To limit the potential for development of resistance, the number of sequential and total seasonal applications are limited. Only one application of Cabrio may be made in the presence of Downey mildew and Late blight, or any disease in cucurbits, before alternating to a fungicide with a different mode of action. Otherwise, two applications may be made before an alternate mode of action is used. The seasonal limits on the number of applications stated above are resistance management limits, as opposed to active ingredient poundage limits.

    The Department conducted the following technical reviews with regard to the registration of Insignia, Headline, and Cabrio EG Fungicides for impacts to human health, nontarget organisms, and the enviromnent. The following review summaries are provided below:

Human Health Review:

    Neither the active ingredient pyraclostrobin nor the formulated products Cabrio EG or Insignia Fungicide were very toxic in acute oral or dermal exposure studies in laboratory animals, nor were they very irritating to the eyes (tested on rabbits). Also, neither pyraclostrobin nor the formulated products including Headline Fungicide were dermal sensitizers (tested on guinea pigs). Pyraclostrobin was moderately toxic by the acute inhalation route of exposure, whereas all three of the formulated products were not very toxic in acute inhalation studies. In regard to acute dermal irritation studies, the active ingredient was moderately irritating to skin (tested on rabbits) and the formulated products Cabrio EG Fungicide and Insignia Fungicide, were mildly irritating. Headline Fungicide, however, was a severe skin irritant and was moderately irritating to the eyes. In addition, the Headline product was moderately toxic by the acute oral route of exposure, but was not very acutely toxic in an acute dermal exposure study. Pyraclostrobin caused neither clinical nor pathological effects in acute and subchronic neurotoxicity studies at the highest doses tested, which were 1,000 milligrams per kilogram body weight per day (mg/kg/day) or 112 mg/kg/day, respectively.

    Pyraclostrobin caused some toxicity in chronic animal feeding studies. In dogs, pyraclostrobin caused diarrhea and clinical chemistry changes in males and females at doses of 10.8 and 11.2 mg/kg/day, respectively. Also observed in females, was a decrease in body weight gain and food intake. The no-observed-effect level (NOEL) for males and females was 5.4 mg/kg/day. In a chronic feeding/oncogenicity study in rats, pyraclostrobin caused. an increase in atrophy of the kidneys and a decrease in body weights and body weight gains in males and females at 9.2 and 12.6 mg/kg/day, respectively. Also, males had an increased incidence of liver necrosis and stomach erosion and ulceration; the NOELs were 3.4 mg/kg/day (males) and 4.7 mg/kg/day (females). In mice, effects were not observed at the highest doses tested, which were 17.2 and 32.8 mg/kg/day, for males and females, respectively. The USEPA Office of Pesticide Programs established a reference dose (RfD) of 0.034 mg/kg/day based on a NOEL of 3.4 mg/kg/day in the chronic feeding/oncogenicity study in rats and an uncertainty factor of 100. This RfD has not yet been adopted by the USEPA's Integrated Risk Information System (IRIS).

    Pyraclostrobin caused some developmental toxicity in the offspring of pregnant rats and rabbits at doses that also caused maternal effects. In a rat oral developmental toxicity study, an increased incidence of dilated renal pelvis and cervical ribs with no cartilage was observed at 50 mg/kg/day; the NOEL was 25 mg/kg/day. Maternal toxicity, characterized by decreased body weights and body weight gain as well as reduced food consumption, was reported at a dose of 25 mg/kg/day; the NOEL was ten mg/kg/day. In rabbits, developmental toxicity characterized by increased resorptions and increased post-implantation loss occurred at ten mg/kg/day; the NOEL was five mg/kg/day. Maternal toxicity consisting of a reduction in body weight gain and food consumption also occurred at ten mg/kg/day, with a NOEL of five mg/kg/day. In a multigeneration reproduction study in rats, pyraclostrobin did not cause either reproductive or parental effects at the highest doses tested which were 29 to 35 mg/kg/day for males and 30 to 36 mg/kg/day for females.

    Pyraclostrobin did not cause oncogenic effects in chronic feeding studies in rats or mice. Pyraclostrobin also was negative in a number of genotoxicity studies. However, due to inadequate dose levels in female mice, the USEPA Cancer Assessment Review Committee (CARC) classified pyraclostrobin into the category "Data are inadequate for an assessment of human carcinogenic potential." The CARC recommended that the registrant should conduct a new study in female mice at an adequate dose level, and this was required by September 30, 2006 as a condition of federal registration.

    The USEPA established tolerances for pyraclostrobin residues in or on stone fruit at 0.9 parts per million (ppm); strawberry (0.4 ppm); grape (2.0 ppm); barley (grain, hay and straw at 0.4, 25.0 and 6.0 ppm, respectively); various corn commodities (0.04-23 ppm); bean (dry at 0.3 ppm); beet (sugar dried pulp at 1.0 ppm); berry (1.3 ppm); citrus (dried pulp at 5.5 ppm); rye (grain and straw at 0.04 and 0.5 ppm, respectively); vegetable (bulb, cucurbit, fruiting, root, tuberous at 0.9, 0.5, 1.4, 0.4 and 0.04 ppm, respectively); wheat (grain, hay and straw at 0.02, 6.0, and 8.5 ppm, respectively) and nut (tree group at 0.04 ppm). The chronic population adjusted dose (cPAD) for pyraclostrobin is 0.034 mg/kg/day and has the same basis as the RfD. The USEPA estimated that the chronic dietary exposure to pyraclostrobin residues would be six percent of the cPAD for the general U.S. population, ten percent for all infants less than one year old and 21% for children one to two years old. This chronic exposure analysis is primarily based on the assumption that most treated crops contain either current or pending tolerance level residues and the use of percent crop treated information, which is based on projected market share information.

    The USEPA conducted a risk assessment for dermal and inhalation exposure of workers to pyraclostrobin from its use on golf course turf grass and a variety of crops for which tolerances have been established, as noted above. For mixers/loaders/applicators, the combined margins of exposure (MOEs) for dermal and inhalation exposures were estimated to range from 1,400 to 6,400 for use on golf courses and from 280 to 6,400 for use on crops. For these estimates, it was assumed that workers wore long-sleeved shirt, long pants, chemical-resistant gloves and shoes plus socks as required on the current pesticide product labels (the Headline product label also requires protective eye wear). For dermal exposure, the USEPA used a dermal absorption factor of 14% and assumed 100% absorption of inhalation exposure. The NOEL used for estimating these MOEs was five mg/kg/day from the rabbit developmental toxicity study (for comparing to short- and intermediate-term dermal and inhalation exposures). For post-application exposures of workers to pyraclostrobin-treated crops, estimated MOEs ranged from 100 to 570, and for golf maintenance workers the MOE range was 280 to 2,300. For golfers, MOEs ranged from 3,800 to 31,000. Generally, the USEPA considers MOEs of 100-fold or greater to provide adequate worker protection and adequate short-term nonworker protection (e.g., golfers).

    There are no chemical specific federal or State drinking water/groundwater standards for pyraclostrobin. 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).

    The available information on pyraclostrobin and the Cabrio and Insignia products indicate that overall the active ingredient and these products (which are identical in formulation) are not very acutely toxic in laboratory animal studies. The eye and skin irritation studies in laboratory animals indicate that Headline Fungicide can cause moderate eye irritation and severe dermal irritation. The potential for adverse effects among handlers, however, should be mitigated by the Headline product label's requirement to use protective eye wear and chemical-resistant gloves plus long-sleeved shirt and long pants, shoes and socks. Although data from chronic and developmental toxicity studies on pyraclostrobin showed that this active ingredient has the potential to cause some toxicity, the expected exposures from its labeled uses should not pose a significant risk to workers or the general public.

Nontarget Organism Review:

    Pyraclostrobin is practically nontoxic to birds and mammals on an acute basis but can be toxic with chronic exposure. It is very highly toxic to fish and aquatic invertebrates, less so to algae and aquatic macrophytes. It is relatively nontoxic to the honey bee.

    Pyraclostrobin is moderately persistent and immobile in soil. It is stable to hydrolysis and soil photolysis but rapidly degrades via photolysis in aqueous solution with a half-life (T 1/2) of roughly two hours. Aerobic and anaerobic soil metabolism T 1/2s are 82 and three days respectively. Results from one supplemental and one invalid aerobic metabolism study were submitted. The supplemental study, conducted with soil/water systems, was deemed invalid due to the sediments being anaerobic. Under the study conditions, pyraclostrobin partitioned into the sediments with a DT50 of one to four days. The mean system DT50 was 17 days. DERs for terrestrial field dissipation studies were submitted for dissipation trials conducted in nine states. The trials examined the dissipation of pyraclostrobin in 16 different plots (various crops plus bare ground). Dissipation T1/2s ranged from 51 to 99 days with a mean of 75 days. In these trials, neither pyraclostrobin nor metabolites leached below three inches deep in ten of the 16 plots and from zero to two inches in three other plots. All but one plot showed parent and metabolites to have moved any deeper than six inches.

Exposure & Risk Assessment Summary:

    Screening level modeling was conducted to estimate nontarget organism pyraclostrobin exposures and risk when Cabrio, Headline, and Insignia were used as labeled. Mammalian and avian food item residues resulting from the highest pyraclostrobin labeled applications exceeded the NOEL from the submitted mouse subchronic study. No other toxicity thresholds were exceeded. Post application runoff modeling showed potential for toxicity to occur to aquatic organisms, particularly invertebrates, but the immobility of pyraclostrobin would indicate that significant widespread impacts are unlikely.

    Aerial application of Cabrio and Headline present an unacceptable level of risk to aquatic organisms. One application directly to surface water at the lowest labeled rate will result in a pyraclostrobin water concentration that far exceeds the lethal concentration for fish, invertebrates, and some algae as reported in the table below.

PONDTOX - DIRECT APPLICATION
SPECIES LC50 NOEC
Rainbow trout EXCEEDED 6X EXCEEDED
Daphnia EXCEEDED 2.4X EXCEEDED
Mysid EXCEEDED 8.8X EXCEEDED
Navicula EXCEEDED 24.7X EXCEEDED
Lemna SAFE SAFE
This program evaluates the toxicity of a direct application of pyraclostrobin to biota in a pond with a surface area of one acre. If the concentration of pyraclostrobin in the water exceeds a toxicity threshold, the model prints EXCEEDED. If the toxicity threshold is not exceeded, the model prints SAFE. Depth of pond = I ft. Application rate = 0.1 lbs AI/acre (lowest labeled rate). The water column concentration of pyraclostrobin is 0.037 mg/L.


Groundwater Technical Review:

Solubility: The solubility of pyraclostrobin is 2.41 mg/L.

Hydrolysis: Pyraclostrobin was stable at pHs 5, 7, 9.

Soil Photolysis: Pyraclostrobin had half-lives of 0.05 and 0.08 days in two ring-labeled studies.

Aqueous Photolysis: Pyraclostrobin had a half-life of 15 days in a sandy loam with a pH of 7.3 and 1.8% organic carbon. Pyraclostrobin had a half--life of 14 days in a sandy loam with a pH of 7.5 and two percent organic carbon. Both had the major degradate BF 500-6 at 13% and 11% respectively. USEPA found these studies acceptable. In a third study, which USEPA found only supplemental, half-lives were 12.6 days in loam, 50.6 days in loam, 94.9 days in a silt loam and 224 days in sandy clay loam. Two major degradates were found: BF 500-3 and BF 500-6 at 18% and 17.78%, respectively. Anaerobic Soil Metabolism: Pyraclostrobin had a half-life of three days in a sandy loam with a pH of 7.5 and 1.5% Organic Carbon. Two major degradates were found: BF 500-3 and BF 500-4 at 96% and 11 %, respectively. Pyraclostrobin had a half-life of three days in a loamy sand soil with pH of 7.2 and 1.4% Organic Carbon. The major degradate found was BF 500-3 at 79.9%.

Aerobic Aquatic Metabolism: Pyraclostrobin had a half-life of five days in water (pH 8.58), five days in sediment (pH of 7.5 and 0.4% Organic Carbon) and seven days in the pond water/coarse sand system. Major degradates were BF 500-3 in the sediment and BF 500-11 at 11%, BF 500-13 at 16% and BF 500-14 at 11% in the water. USEPA, however, found this study unacceptable and required a new study. Two studies were done: pond water/sandy loam (0.8% OC) and a pond-river water/loam (8.3% OC). Pyraclostrobin had a half-life of one to four days in water and 8.8 days in the entire system. Major degradates were BF 500-3 in the sediment at 12% in the first study and 65.7% in the second study. USEPA found these studies supplemental and required a new study.

Field Dissipation: Pyraclostrobin dissipated with a half-life of 51-99 days in the U.S. sites and 98-178 days in the Canadian sites. Major degradates were BF 500-3, BF 500-6, and BF 500-7 at the U.S. sites, and BF 500-6 at the Canadian site. Computer modeling was not run on pyraclostrobin or the degradates because of the extremely high KocS as reported in the table below. Chemicals with KocS in a range this high do not leach and as such would not impact groundwater resources.

Adsorption/Desorption:
Soil
Desorption Kocs
Type % OC pH Parent BF 500-3 BF 500-5 BF 500-6 BF 500-7
sandy 0.8 5.2 1200 45700      
loamy sand 1.9 5.6 16984 27000      
sandy loam 1.8 7.3 15444 38400      
loamy sand 0.5 5.9 10200 69900      
loam 0.6 5.3 13833 76500      
sandy clay loam 3.9 7.6 17462 141000      
loamy sand 2.5 5.8     99. 91000 83000
sandy loam 1.5 705     787 129000  
loamy sand 1.1 6.5     1135 126000 101000
loamy sand 0.4 5.8     2688 151000 2050000
loam 0.5 5.2     2386 250000 1660000
sandy clay loam 3.4 7.5     3849 34000 37000


Pesticide Product Registration Summary:

    The Department has reviewed your application to register Insignia (EPA Reg. No. 7969-184); Headline (EPA Reg. No. 7969-186); and Cabrio EG Fungicide (EPA Reg. No. 7969-187) containing the new active ingredient pyraclostrobin. In order for the Department to register these products in New York State, the following conditions are required in regard to labeling for Cabrio EG and Headline Fungicide to protect aquatic resources in New York State. The following statement must appear on both the front panel of the product label and under the product "Restrictions and Limitations" section: "No aerial application in New York State except as permitted under FIFRA Section 24(c), Special Local Needs Registration." The Department will allow stickering of existing container labeling as an interim measure until new labeling can be produced.

    Please also note that per the human health reviewer recommendation, the Department will require BASF Corporation to submit either a USEPA Data Evaluation Record report or review of the supplemental carcinogenicity study in female mice that is required to be submitted to the USEPA by September 30, 2006 as a condition of federal registration. While there is no evidence that pyraclostrobin is carcinogenic, the issue regarding this potential has not yet been fully resolved by the USEPA.

    Enclosed for your record is a copy of the stamped accepted labeling and the Certificate of Registration for Insignia (EPA Reg. No. 7969-184); Headline (EPA Reg. No. 7969-186); and Cabrio EG Fungicide (EPA Reg. No. 7969-187). Please note that a proposal by BASF Corporation, or any other registrant, to register a product that contains pyraclostrobin for additional food crops, or any other labeled uses that are likely to increase the potential for significant impact to humans, nontarget organisms, or the environment, would constitute a major change in labeled (MCL) use pattern. Such an application must be accompanied by a new application fee and meet the requirements listed in Appendix 1.B. of "New York State Pesticide Product Registration Procedures" (August 1996). Such information, as well as forms, can be accessed at our website as listed in our letterhead.

    Please be aware that any unregistered product may not be sold, offered for sale, distributed, or used in New York State.

    If you have any questions on this matter, please contact Paula McBath, of my staff, at (518) 402-8768.

Sincerely,

Maureen P. Serafini
Director
Bureau of Pesticides Management

Enclosure
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