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hexythiazox (Savey) Major Change in Labeling 9/01


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
E-Mail: ppr@gw.dec.state.ny.us

September 4, 2001

CERTIFIED MAIL
RETURN RECEIPT REQUESTED


Ms. Rebecca A. Lamas
Registration Specialist
Gowan Company
P.O. Box 5569
Yuma, AZ 85366-5569

Dear Ms. Lamas:

Re: Registration of a Major Change in Labeling for the Active Ingredient Hexythiazox, Contained in the Pesticide Product Savey Ovicide/Miticide 50-WP (EPA Reg. No. 10163-208)

    The New York State Department of Environmental Conservation (the Department) has reviewed your application, received October 6, 2000, and additional information, received December 6, 2000, to register the above-mentioned product in New York State. The label contains revised directions for use on apples and adds use on strawberries and stone fruit. The revisions constitute a major change in labeling for hexythiazox in New York State.

    The application was deemed complete for purposes of review on April 9, 2001 and a registration decision is due by September 6, 2001.

    The Department has reviewed the information supplied to date in support of registration of the major change in labeling application of Savey Ovicide/Miticide 50-WP (EPA Reg. No. 10163-208).

    The New York State Department of Health (DOH) stated that neither hexythiazox nor the formulated product was very acutely toxic in laboratory animal studies. Hexythiazox did not cause teratogenic effects in laboratory animals, nor did it cause genotoxic effects. Some parental and offspring effects were observed in a two-generation rat reproduction study (decreased pup weight during nursing, slight delay in hair growth and/or eye opening). Other toxicological data indicate that hexythiazox caused some toxicity in chronic animal feeding studies. The United States Environmental Protection Agency (USEPA) established a reference dose (RfD) of 0.025 milligrams per kilogram body weight per day (mg/kg/day) based on a no-observed-effect level (NOEL) of 2.5 mg/kg/day in a chronic dog feeding study (hypertrophy of the adrenal cortex in males and females and hematological effects in males) and an uncertainty factor of 100. Hexythiazox caused an increased incidence of liver tumors in female mice. No chemical-related oncogenic effects were reported in male mice or in male and female rats. The USEPA classified hexythiazox as a Group C "possible human carcinogen" and calculated a cancer potency slope factor for this compound of 0.022 (mg/kg/day)-1. Previously, the USEPA had calculated a cancer potency slope factor of 0.039 (mg/kg/day)-1. A current search of the toxicological literature did not find any significant new information on the toxicity of hexythiazox.

    The USEPA established tolerances for hexythiazox residues in or on apples at 0.5 parts per million (ppm), strawberries at 3.0 ppm and stone fruit (except plums) at 1.0 ppm. The USEPA estimated that chronic dietary exposure to residues from these fruits would be less than 1.0 percent of the chronic population adjusted dose (cPAD) of 0.025 mg/kg/day for both the general U.S. population and for all infants less than one year old. Based on a chronic dietary exposure estimate of 1.0 x 10-5 mg/kg/day and the cancer potency slope factor of 0.022 (mg/kg/day)-1, an increased lifetime cancer risk of 2.54 x 10-7 can be calculated for the general U.S. population. This estimated risk is below the level the USEPA considers negligible (1 x 10-6) for additional lifetime cancer risk. The chronic dietary exposure analysis for both non-cancer and increased cancer risk was based on percent crop treatment information and residues anticipated from proper use.

    The USEPA also evaluated worker risks from the use of Savey Ovicide/Miticide 50-WP. For mixer/loaders an average daily inhalation/dermal exposure of 0.0367 mg/kg/day was estimated, based on applications of 71 grams of hexythiazox per acre to 350 acres per day for an average working period of 15 days per year. When this exposure estimate is compared to the NOEL from a 90-day rat feeding study (5.4 mg/kg/day), a margin of exposure (MOE) of about 150 can be calculated. Generally, an MOE of 100-fold or greater is considered adequate for worker protection. Additionally, a lifetime average daily dose for a mixer/loader of 0.00045 mg/kg/day corresponded to an increased cancer risk of 9.9 x 10-6. This value is within the general USEPA acceptable level of comparison (1 x 10-4 or less) for occupational exposures. There are no chemical-specific federal or State drinking water/groundwater standards for hexythiazox. Based on its chemical structure, hexythiazox falls under the 50 micrograms/liter (&g/L) New York State drinking water standard for "unspecified organic contaminants" (10 NYCRR Part 5 - Public Water Systems). Using the USEPA cancer potency slope factor of 0.022 (mg/kg/day)-1 and 6 NYCRR Part 702.4 procedures for deriving ambient water quality standards and guidelines based on oncogenic effects, the value associated with a one in one million increased lifetime cancer risk is 1.6 &g/L for hexythiazox.

    Neither hexythiazox nor Savey Ovicide/Miticide 50-WP was very toxic following acute exposure in laboratory animal studies. Hexythiazox caused some toxicity in chronic animal feeding studies, but did not cause reproductive or teratogenic effects. This chemical did cause liver tumors in female mice and the USEPA classified hexythiazox as a "possible human carcinogen." Savey Ovicide/Miticide 50-WP is currently registered in New York State for use on apples and pears. The new label contains directions for use on strawberries and stone fruits and increases the allowable application rate for apples by as much as two-fold. Both a dietary and occupational cancer risk assessment conducted by the USEPA indicated that the increased lifetime cancer risk to the public and workers generally would not exceed USEPA acceptable levels. In addition, estimated non-cancer risks to workers and the public also are low.

    The USEPA conditionally registered Savey Ovicide/Miticide 50-WP pending completion of several studies including a repeated dose dermal toxicity study and an in vivo mouse micronucleus test. The Department requests that Gowan Company submits the USEPA Data Evaluation Record reports for these studies when completed.

    The Department's Division of Fish, Wildlife & Marine Resources' Bureau of Habitat (BOH) concluded that the new strawberry and stone fruit uses of Savey Ovicide/Miticide 50-WP should not adversely impact the fish and wildlife resources of New York State. Savey Ovicide/Miticide 50-WP is not toxic to fish, invertebrates, mammals, birds, or nontarget insects, when applied by ground equipment according to BOH's aquatic and terrestrial models.

    The BOH raised some concerns regarding the potential for adverse effects to non-target aquatic life if Savey Ovicide/Miticide 50-WP were to be aerially applied directly to surface waters at the maximum application rate of 6 ounces per acre. Direct Savey application to surface waters at the 6 ounce per acre rate would exceed the BOH aquatic life protective criteria for aerially applied products. However, the BOH's concerns were allayed as a result of conversations with growers and discussions regarding the actual application practices of hexythiazox to apples.

    The Pesticide Compliance Section summarized the environmental fate parameters as follows:

Hydrolysis: The half-lives were 8.9 x 104 hours at 22oC and pH 9; this is greater than 10 years. The half-lives at pHs 5 and 7 were longer. Therefore, this pesticide can be considered stable under hydrolysis conditions.

Aqueous Photolysis: The half-life was 400 hours (16.6 days) in natural sunlight; no major degradates were formed.

Soil Photolysis: The half-life was 116 days in natural sunlight.

Aerobic Metabolism: The EPA Pesticide Fact Sheet states that the half-life ranged from 17-35 days under laboratory conditions. The registrant reports that hexythiazox had a half life of 8 and 25 days at 15oC in sandy loam and clay loam soils; 6 and 14 days at 25oC. Several hydroxylated and -oxo thiazolidine metabolites were found.

Anaerobic Metabolism: Hexythiazox had a half-life of 120 days at 25oC. Several hydroxylated and -oxo thiazolidine metabolites were found. This study was not required for registration in orchards; it is not known whether EPA approved the study results.

Adsorption/Desorption: Registrant submitted Kocs were 13,621 in sand, 5747 in silt loam, 3234 in sandy loam and 2598 in clay loam. In the February 2, 1996 memorandum, a Koc of 3190 was derived using the submitted Kd value of 31.9 in a sandy loam soil with 1.7% OM. The calculation used was Koc = Kd/0.0058 x %OM).

Field Dissipation: The EPA Pesticide Fact Sheet states that the half-life ranged from 5 to 15 weeks. The registrant reports that the half-life was 15 weeks in Delaware soil, 14 weeks in a North Carolina soil, 10 weeks in an Illinois soil, 5 weeks in a Mississippi soil, and 26 weeks in a California soil. All were at 6 oz product/yr.

Computer Modeling: Running LEACHM on Riverhead soil for using a Koc of 3190, a half-life of 35 days (the maximum) and an application rate of 3 oz ai/acre/year (maximum use rate), the model projected no leaching of the active ingredient.

    The Pesticide Compliance Section concluded that Savey Ovicide/Miticide 50-WP should not impact groundwater in New York State when used according to label directions for both apples and pears. Multiple computer simulations of the vadose zone fate of hexythiazox confirmed the EPA characterization that hexythiazox does "not have significant vertical mobility" and is "not likely to leach and contaminate groundwater." Hexythiazox does not behave like most other new active ingredients, and fits poorly into the standard computer model. Due to the extremely low solubility and hydrophobic nature of hexythiazox, it has a tendency to be sequestered on all available solid surfaces. Therefore, the lessened availability of soil particulates and lowered total surface area in a sandy soil, as opposed to a finer grained soil, are of a greater concern than the amount of organic carbon. It would appear from the adsorption/desorption study submitted that hexythiazox is approximately twice as likely to leach in a sandy soil than in the sandy loam soil modeled. However, given the Koc and the application rate, it is the Pesticide Compliance Section's opinion that this product will not have a negative impact on ground or surface water when used as labeled.

    The Department concludes that Savey Ovicide/Miticide 50-WP 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 for Savey Ovicide/Miticide 50-WP (EPA Reg. No. 10163-208).

    Enclosed is your New York State stamped "ACCEPTED" label.

    If you have any questions, please contact Ms. Jeanine Broughel, 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
G. Good/W. Smith - Cornell University, PMEP