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bifenazate (Acramite 50WS) Major Label Change 10/02

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

October 21, 2002

CERTIFIED MAIL
RETURN RECEIPT REQUESTED


Ms. Theresa Hass
State Registration Coordinator
Crompton Manufacturing Company, Inc.
74 Amity Road
Bethany, Connecticut 06524-3402

Dear Ms. Hass:

Re: Registration of One New Pesticide Product, Acramite 50WS, (EPA Reg. No. 400-503) Which Represents a Major Change in Labeled Use for the Active Ingredient Bifenazate

The New York State Department of Environmental Conservation (Department) has reviewed the application, received May 10, 2002, from Crompton Manufacturing Company, Inc. (formerly Uniroyal Chemical Company, Inc.), to register the above-mentioned product in New York State. The application was deemed complete for purposes of review on July 2, 2002 and a registration decision is due by November 29, 2002.

Acramite 50WS contains the active ingredient bifenazate (hydrazine carboxylic acid, 2-(4-methoxy-[1,1,-biphenyl]-3-yl) 1-methylethyl ester) and is labeled "for agricultural use only" to control mites on a variety of fruit crops, such as apples, strawberries, grapes and plums, as well as hops and cotton. Bifenazate is currently registered in the State for use on ornamental plants. The use of bifenazate on food crops represents a major change in labeled use pattern in New York State.

HEALTH EFFECTS:

The toxicity of bifenazate was previously reviewed for registration of the pesticide product Floramite. Neither bifenazate nor the formulated product Acramite 50WS was very toxic in acute oral, dermal or inhalation toxicity studies in laboratory animals, nor were they very irritating to the eyes or skin. Whereas the formulated product was not a dermal sensitizer, the active ingredient bifenazate gave mixed results; bifenazate was negative in the Buehler sensitization test, but was positive in the Magnusson/Klingman sensitization test.

Bifenazate caused some toxicity in subchronic dermal and feeding studies in laboratory animals. In a 21-day dermal study in rats, bifenazate caused a decrease in body weights in females, an increase in urinary ketones and protein, a decrease in urinary volume and an increased incidence of extramedullary hematopoiesis in the spleen of both sexes at 400 milligrams per kilogram body weight per day (mg/kg/day); the no-observed-effect level (NOEL) was 80 mg/kg/day. In a 90-day feeding study in rats, decreased body weight gain, increased liver weights, and histopathological changes in the liver, spleen and adrenal cortex (males only) were reported at dose levels of 27.7 mg/kg/day and 16.3 mg/kg/day in males and females, respectively.

The respective NOELs were 13.8 mg/kg/day and 3.2 mg/kg/day. In a 90-day dog feeding study, changes in hematological parameters, increased bilirubin in urine, and histopathologic effects in the liver were reported in males at 10.4 mg/kg/day; the NOEL was 0.9 mg/kg/day. An increase in the absolute liver weight, changes in hematological parameters and histopathology of the liver were reported in females at 10.7 mg/kg/day; the NOEL was 1.3 mg/kg/day.

Bifenazate also caused some toxicity in chronic animal feeding studies. In a one-year dog feeding study, bifenazate caused changes in hematological and clinical chemistry parameters and histopathological effects in the bone marrow, liver and kidney at a dose level of 8.9 mg/kg/day for males and 10.4 mg/kg/day for females; the respective NOELs were 1.0 mg/kg/day and 1.1 mg/kg/day. In a chronic feeding/oncogenicity study in mice, decreased body weight and body weight gain were reported in females at a dose level of 35.7 mg/kg/day; the NOEL was 19.7 mg/kg/day. Hematological effects and decreased kidney weights in males were seen at a dose level of 15.4 mg/kg/day; the NOEL was 1.5 mg/kg/day. In a chronic feeding/oncogenicity study in rats, decreased body weight, body weight gain and food consumption were reported in males and females at a dose level of 9.7 mg/kg/day; the NOELs were 3.9 mg/kg/day (males) and 4.8 mg/kg/day (females). The United States Environmental Protection Agency (USEPA) Office of Pesticide Programs established a reference dose of 0.01 mg/kg/day for bifenazate based on the NOEL of 1.0 mg/kg/day from the chronic dog feeding study and an uncertainty factor of 100. This same value was used as a chronic population adjusted dose (cPAD) for evaluating dietary risks.

Bifenazate 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 bifenazate as "not likely" to be a human carcinogen.

Bifenazate did not cause developmental effects in offspring of either pregnant rabbits or rats administered this compound during organogenesis at doses up to 200 and 500 mg/kg/day, respectively. Maternal toxicity in rats, which was characterized by reduced body weight gain, reduced food consumption and lower absolute body weight, occurred at exposures of 100 mg/kg/day; the NOEL was 10 mg/kg/day. No maternal toxicity was observed in the rabbit developmental study. In a two-generation reproduction study in rats, no reproductive effects were reported at 16.4 mg/kg/day for males and 18.3 mg/kg/day for females (the highest doses tested). Parental toxicity consisted of a reduction in body weight, body weight gain and food consumption at a dose level of 6.5 mg/kg/day for males and 7.4 mg/kg/day for females; the respective NOELs were 1.6 mg/kg/day and 1.8 mg/kg/day.

The USEPA established the following tolerances for bifenazate: 15 parts per million (ppm) for hops, 0.75 ppm each for grapes and pome fruit, 1.2 ppm for wet apple pomace, 1.7 ppm for nectarines and peaches, 0.3 ppm for plums and 1.5 ppm for strawberries. The USEPA estimated that chronic dietary exposure to these residues would be 16 percent of the cPAD of 0.01 mg/kg/day for the general US population, 39 percent for children one to six years old and 52 percent for all infants less than one year old. This chronic exposure analysis is based on the assumption that 100 percent of crops are treated and contain tolerance level residues. Actual residues and resulting exposure levels are expected to be less than these estimates.

The USEPA reported the results of an occupational risk assessment for dermal and inhalation exposures to bifenazate from use on cotton and hops. These crops were chosen because they represent a worst-case scenario of exposure to bifenazate. It was assumed that bifenazate was mixed, loaded, and applied to between 40 and 1,200 acres per day, depending on application methods. For determining margins of exposure (MOEs), the USEPA compared estimated short-term dermal and inhalation exposures to NOELs of 80 mg/kg/day and 10 mg/kg/day from the 21-day rat dermal toxicity study and the rat developmental toxicity study, respectively. For commercial handlers and applicators, the combined MOEs for dermal and inhalation exposures were estimated to be 470 and above. These estimates assumed that all workers wore long-sleeved shirt and pants, shoes plus socks as per label requirements. The MOEs for post-application occupational exposures (hand thinning, hand harvesting, and scouting activities) were estimated to be 120 and above and were based on dermal exposures. The exception was for certain high foliar contact activities with grapes (i.e., girdling, cane tying, and turning) where the MOE was estimated to be 62. To address this situation, the USEPA established a five-day restricted-entry interval (REI) to reach the target MOE of greater than or equal to 100. Generally, the USEPA considers MOEs of 100-fold or greater to provide adequate worker protection.

There are no chemical specific federal or State drinking water/groundwater standards for bifenazate. Based on its chemical structure, bifenazate 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 bifenazate and Acramite 50 WS indicates that they are not very acutely toxic in laboratory animal studies. In addition, bifenazate does not appear to be oncogenic, genotoxic, or to cause developmental/reproductive toxicity. Although data from subchronic and chronic studies on bifenazate showed that this chemical has the potential to cause certain hematological changes and other clinical effects at relatively low doses, the proposed uses of the product do not pose significant risks to workers or the general public.

ECOLOGICAL EFFECTS:

Acramite is labeled for pest mite control on apples, cotton, grapes, hops, nectarines, peaches, pears, plums, and strawberries. One application may be made per year at 0.75 to 1.0 lbs Acramite per acre, in at least 50 gallons of water, equaling 0.375 to 0.5 lbs bifenazate per acre. It may be applied with ground equipment only and may not be applied through irrigation systems. Bifenazate is highly specific for tetranychid (spider) mites and, according to the UNIROYAL Reduced Risk Rational document included in the data package, has low toxicity to predatory mites and beneficial insects. The label suggests Acramite may be used in combination with most biological control organisms available for mite control and lists 11 predatory mite and insect species that are suitable for such strategies.

Bifenazate, Hydrazine carboxylic acid, 2-(4-methoxy-[1,1'-biphenyl]-3-yl)methylethyl ester, belongs to the carbazate chemical class. Its water solubility is 3.8 mg/L. With a KOW of 2512 bifenazate is not likely to bioaccumulate. Its vapor pressure is low at 1x10-7 mmHg so volatilization will not contribute significantly to its dissipation.

Bifenazate's mode of action is unknown at present and is under investigation.

Bifenazate is practically non toxic to birds and mammals on an acute basis but can cause chronic toxicity. It is moderately toxic to honeybees with an LD50 of 7.8 ug/Bee. It is highly toxic to all aquatic organisms tested except Mysid shrimp for which it is very highly toxic.

Bifenazate degrades rapidly in the environment via all pathways/mechanisms tested except by anaerobic microbial metabolism. All bifenazate metabolites seem similarly short-lived with the exception of 4-methoxybiphenyl known as D1989 which, in an aerobic soil metabolism study, represented 26.8% of the applied parent compound three days post application, and 21.9% at 28 days. In contrast to statements made in the applicants Reduced Risk Rational document, the USEPA Environmental Fate And Effect Division , EFED, December 2001 bifenazate risk assessment reports an aerobic soil Half-life for D1989 of 60 days. No other degradation data for D1989 seems to have been generated. A column leaching study shows it to be very mobile in a sandy loam soil from California, mobile in silt loam, silty clay loam, and sandy loam soils from Ohio, and to have low mobility in loam sediment from Ohio. One toxicity study with Daphnia was conducted which shows it to be twice as toxic as the parent compound. Coarse, screening-level terrestrial food item residue and aquatic runoff exposure modeling was conducted for both bifenazate and the D1989 metabolite. For the parent compound, avian and mammalian terrestrial food item residues were estimated at two levels, the first at the maximum levels likely to occur immediately post application, the second at more typical, more frequently observed concentrations. Acute and chronic toxicity predictions are included. Only the upper end of the estimated bifenazate runoff aquatic loading range is included here.

For D1989 no acute toxicity thresholds were reached so only chronic predictions at maximum terrestrial food item residue levels are reported. Only the upper end of the aquatic runoff range is reported.

For both parent and metabolite, it was assumed that no target plant interception occurred for both terrestrial and aquatic scenarios. Additionally, it was assumed that all of the runoff water reached the PONDTOX model pond. D1989 soil mobility was maximized by setting its KOW at 100. The only toxicity data available for D1989 shows it to be twice as toxic to Daphnia as the parent compound. For modeling purposes, it was assumed that it is twice as toxic to all other test species as well.

No acute mammalian toxicity thresholds were exceeded with bifenazate. Numerous chronic feeding and/or reproductive NOELs and one LOEL were exceeded at maximum residue levels. The LOEL and several NOEL accedences drop out when residues are recalculated at "typical" concentrations. A similar pattern resulted for avian dietary exposure estimates.

Direct application of bifenazate to water at the maximum label rate results in a water concentration that exceeds the Mysid shrimp LC50 and all NOECs except for Lemna. The maximum likely bifenazate runoff loading to the model pond resulted in water concentrations that exceeded the Mysid shrimp NOEC at all depths and the Rainbow trout NOEC in the one-foot depth, no LC50s were exceeded.

With D1989, no avian or mammalian acute feeding thresholds were exceeded (model results are not included here). Chronic avian and mammalian feeding modeling yielded similar results. No LC50 or LOEC thresholds were exceeded for either group. Five mammalian and three avian chronic NOEC thresholds were exceeded. D1989 PONDTOX results are similar to those for the parent compound except D1989 runoff results in slightly more Rainbow trout Early Life Stage toxicity. As with bifenazate, however, no LOEL thresholds were exceeded.

Fish and wildlife resources are not likely to be adversely affected by labeled use of Acramite 50WS. The assumptions and conditions modeled in this review are highly conservative, worst-case estimates that don't account for the rapid environmental degradation of bifenazate. Even under these exaggerated conditions, toxicity thresholds are only slightly exceeded. The minor effects predicted herein are not likely to occur in the field.

GROUNDWATER IMPACTS:

Hydrolysis: USEPA found that this study was supplemental and could be upgraded to meet the Subdivision N guidelines (they did not identify degradates that were present at >10%). Bifenazate has a half-life of 9.1 days at pH 4, 5.4 days at pH 5, 0.8 days at pH 7, and 0.08 days at pH 9.

Soil Photolysis: USEPA found this study to be acceptable. Bifenazate has a half-life of <0.5 hour. Due to the rapidity of degradation in both the irradiated and dark controls, it could not be determined if photodegradation occurred. Degradate D3598 was a maximum of 84.3% at two hours. Degradate D1989 was a maximum of 11.2% at three days.

Aqueous Photolysis: USEPA found this study to be acceptable. Bifenazate has a corrected half-life of 16.2 hours at pH 5. Degradate D3598 was a maximum of 74.4% at 27.9 hours. Degradate D1989 was a maximum of 13.8% at 53.8 hours. Degradate D9472 was 15.9% at 150.5 hours.

Aerobic Soil Metabolism: USEPA found this study to be acceptable. Bifenazate degraded immediately upon application to D3598. Degradate D3598 was 92% at 0.5 hours, then degraded with a half-life of 7.3 hours. Degradate D1989 was 26.8% at three days.

Anerobic Aquatic Metabolism: The phenyl ring-labeled bifenzate dissipated with a registrant-calculated half-life of 77.9 days in a flooded loam. Bifenazate has a half-life of 77.9 days. Degradate A1530 was 24.8% at 294 days, and D3598 was 14.7% at 231 days.

Column Leaching: USEPA found this study to be acceptable. Bifenazate has low mobility in sandy loam, and is immobile in silt loam and clay loam soils.

Adsorption/Desorption: USEPA found this study to be acceptable. The adsorption Kocs were 3905, 3011, 3962, 3725 and 6189 in silt loam, sandy loam, silty clay loam, sandy loam and loam respectively. The desorption Kocs were 5014, 7074, 5749, 5010 and 7453 respectively.

Terrestial Field Dissipation: USEPA found this study to be partially acceptable. In NC, the reported half-life of five days is of questionable validity, because no degradates were detected other than D1989 at <0.03 ppm at four hours, and at four, seven, and 14 days post-treatment, and the storage stability data may not be adequate. USEPA found a second study to be partially acceptable because there was a lack of observable degradates or compound leaching. In Washington, the half-life was reported to be five days.

Computer Modeling: Running LEACHM on Riverhead soil using an application rate of 0.75 lb ai/a/year, a Koc of 5010, and a half-life of less than one day, the model projected no leachate (because of the short half-life).

Given the low application rate of 0.75 lb ai/a/app, and the very high Koc values, this product, when used as labeled, will not have a negative impact on ground or surface water in New York State.

The Department concludes that Acramite 50WS 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 the major change in labeling application of Acramite 50WS (EPA Reg. No. 400-503) which contains the active ingredient bifenazate.

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

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
Division of Solid & Hazardous Materials

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