|New York State Department of Environmental
Division of Solid & Hazardous Materials
50 Wolf Road, Albany, New York 12233-7254
Phone: (518) (518) 457-6934FAX: (518) 457-0629
|March 23, 2000|
RETURN RECEIPT REQUESTED
Ms. Charlotte A. Sanson
P.O. Box 13528
Research Triangle Park, NC 27709-3528
Dear Ms. Sanson:
Re: Registration of a Major Change in Labeled Use Pattern for the Active Ingredient Kresoxim-Methyl Contained in the Pesticide Product Sovran® Fungicide (EPA Reg. No. 7969-154)
The New York State Department of Environmental Conservation ("The Department") has completed review of your application and supplemental information supplied to date regarding registration of the referenced pesticide product in New York State. Sovran® Fungicide (EPA Reg. No. 7969-154) contains the active ingredient kresoxim-methyl: (methyl (E)-2-methoxyimino-2-[2-(o-tolyloxymethyl)phenyl] acetate).
Sovran® Fungicide, containing 50.0% kresoxim-methyl, is a water-dispersible granule formulation labeled for control of certain pathogens on apples, grapes, pears and other pome fruits, and pecans. The maximum seasonal application rate for Sovran® Fungicide is 1.6 pounds (25.6 ounces)/acre/season which is equivalent to 0.80 pounds kresoxim-methyl/acre/season.
Cygnus® Fungicide, registered on December 3, 1999, represented the first product containing the active ingredient kresoxim-methyl registered in New York State. Cygnus® was labeled for use on greenhouse-grown ornamental plants. The proposed use of Sovran® Fungicide on food crops represents a major change in labeled (MCL) use pattern for kresoxim-methyl in New York State.
The subject application and data package were deemed administratively complete on August 31, 1999 and complete for purposes of technical review on October 29, 1999. Pursuant to the review timeframe specified in ECL §33-0704.2, a registration decision date of March 27, 2000 was established.
The Department conducted toxicological, ecological effects and environmental fate risk assessments for kresoxim-methyl and the Sovran® formulation.
TOXICOLOGICAL RISK ASSESSMENT:
Neither kresoxim-methyl nor the Sovran® product were very toxic following acute exposure in laboratory animal studies. Neither of them were skin sensitizers. Both caused mild irritation to rabbit eyes. Kresoxim-methyl also was not very toxic following chronic exposures and did not cause reproductive or teratogenic effects. The United States Environmental Protection Agency (USEPA) calculated an oral reference dose (RfD) for kresoxim-methyl of 0.36 milligrams per kilogram body weight per day (mg/kg/day) based on the no-observed-effect level (NOEL) of 36 mg/kg/day in a two-year rat feeding study and an uncertainty factor of 100. This value has not yet been placed in USEPA's Integrated Risk Information System.
Kresoxim-methyl caused liver tumors (hepatocellular carcinomas) in both sexes of rats exposed over their lifetime, but did not cause an increase in tumors in mice nor was it genotoxic. The USEPA's Health Effects Division Cancer Assessment Review Committee classified kresoxim-methyl as "a likely human carcinogen" and calculated a cancer potency slope factor for this compound of 0.00290 (mg/kg/day)-1.
The USEPA established tolerances for the residues of kresoxim-methyl in or on pome fruit at 0.5 parts per million (ppm), grapes at 1.0 ppm and pecans at 0.15 ppm. The USEPA estimated that chronic dietary exposure from kresoxim-methyl use on crops would be 0.00019 mg/kg/day for the general United States population and 0.00087 mg/kg/day for the most highly exposed sub-group, non-nursing infants. These exposure estimates represent 0.05 percent and 0.2 percent of the oral RfD, respectively. Based on the chronic dietary exposure estimate and the cancer potency slope factor of 0.00290 (mg/kg/day)-1, an increased lifetime cancer risk of 5.5 x 10-7 can be calculated for the general U.S. population. The chronic dietary exposure analysis was based on the assumption that 100 percent of all commodities for which tolerances are established are treated and that they contain residues anticipated from proper label use.
The USEPA also evaluated worker risks from use of the Sovran® product. For mixer/loader, applicators and mixer/loader/applicators, average daily exposure was estimated to be 0.0077, 0.046 and 0.054 mg/kg/day, respectively, based on application to 40 acres per day for a period of 14 days, four times per year. When these exposure estimates are compared to the NOEL from a 90-day rat feeding study (146 mg/kg/day), margins of exposure of about 19,000, 3,200 and 2,700, respectively, can be calculated. Generally, margins of exposure 100-fold or greater are considered adequate. Lifetime average daily doses of 0.00059, 0.0035 and 0.00041 for mixer/loaders, applicators and mixer/loader/applicators, respectively, correspond to increased cancer risks of 1.7 x 10-6, 1.0 x 10-5 and 1.2 x 10-5. These values are within the general USEPA acceptable level of comparison (1.0 x 10-4 or less) for occupational exposures. The estimated cancer risks for workers involved in harvesting (assumed to work for 90 days per year) and thinning (assumed to work for 60 days per year) of grapes were estimated by USEPA to be 6.1 x 10-5 and 1.2 x 10-4, respectively. The margins of exposure for harvesters and thinners are about 860 and 300, respectively, when average daily dose is compared to the NOEL from the 90-day rat feeding study (146 mg/kg/day). For thinners, the cancer risk estimate suggests that exposures are slightly above USEPA's acceptable level, but they indicated that the exposure scenario used is highly unlikely and probably overestimates risks.
The data from the environmental fate studies on kresoxim-methyl indicate that this chemical and some of its degradates may have the ability to leach through soil and contaminate groundwater. In addition, the Sovran® Fungicide label contains a "Ground Water Advisory" which states that "the use of this chemical in alkaline areas where soils are permeable, particularily where the water table is shallow, may result in groundwater contamination."
There are no chemical specific federal or State drinking water/groundwater standards for kresoxim-methyl or its degradates. Based on their chemical structure, kresoxim-methyl and its degradates fall under the 50 micrograms per liter ( g/L) general New York State drinking water standard for "unspecified organic contaminants" (10 NYCRR Part 5, Public Water Systems). The New York State drinking water standard for the sum of "unspecified organic contaminants" and "principal organic contaminants" is 100 micrograms per liter. Using the USEPA cancer potency slope factor of 0.00290 (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 12 g/L for kresoxim-methyl.
Neither kresoxim-methyl nor the Sovran® product were very toxic following acute exposure in laboratory animal studies. Kresoxim-methyl also was not very toxic following chronic exposures and did not cause reproductive or teratogenic effects. This chemical did cause liver tumors in rats exposed over their lifetime and the USEPA classified kresoxim-methyl as "a likely human carcinogen." 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 and estimated non-cancer risks to workers are also low. While the estimated risks posed by Sovran® are within the USEPA acceptable range, the New York State Department of Health (NYSDOH) has concerns for registering a pesticide product that has carcinogenic potential unless either the needs for the product are significant or it replaces products that pose greater risks. Consequently, BASF submitted information that compares the risks and benefits of Sovran® to other products registered for the same use.
The comparison of fungicides provided by BASF was most relevant in determining whether or not registration of Sovran® would increase the overall risks to workers and the general public from use of fungicides on apples, grapes and other labeled crops. The comparison considered a number of different fungicides, but indicated that the active ingredients kresoxim-methyl would most likely replace are captan, mancozeb, sulfur and triphenyltin hydroxide. Triphenyltin hydroxide appears to be used primarily on pecans, which are not grown in New York State. Benomyl was also identified as being used on apples to a significant extent and kresoxim-methyl could serve as a replacement for this compound. Of these four primary alternate fungicides, the USEPA classified captan and mancozeb as B2 (probable human) carcinogens, benomyl as a C (possible human) carcinogen and has not classified sulfur. The cancer potency slope factors (q1*) for benomyl, captan and mancozeb are 4.2 x 10-3, 2.4 x 10-3 and 6.01 x 10-2 (mg/kg/day)-1, respectively. The USEPA classified kresoxim-methyl as a likely human carcinogen with q1* of 2.9 x 10-3. The USEPA established oral reference dose values of 0.05, 0.13, 0.36 and 0.003 mg/kg/day for benomyl, captan, kresoxim-methyl and mancozeb, respectively. No RfD has been developed by the USEPA for sulfur because no tolerances are required for this compound. In addition to the toxicological characteristics of kresoxim-methyl and its primary alternatives, the application rates for these compounds can also be compared. According to the registrant, the average application rates for benomyl, captan, kresoxim-methyl and mancozeb are 0.25 - 0.31, 2.0 - 4.0, 0.1 - 0.125 and 2.25 - 3.0 pounds active ingredient per acre, respectively. The average application rate for sulfur was stated to be 8.0 pounds per acre. Also, the tolerances for these alternative fungicides are 14 to 50-fold higher for apples and seven to 50-fold higher for grapes, which suggests that kresoxim-methyl residues on these two crops would be correspondingly lower. Consequently, the use of kresoxim-methyl on crops instead of these alternatives would likely reduce dietary exposure and risks.
Kresoxim-methyl has some carcinogenic potential and Sovran® is labeled for use on several food crops grown in New York State, most notably, apples and grapes. With the exception of sulfur, the currently registered fungicides that Sovran® is likely to replace also have some carcinogenic potential. Based on a simple comparison of RfD information, kresoxim-methyl appears to be somewhat less toxic than these alternatives (although comparable data for sulfur were not available). In addition, the application rate and tolerances for kresoxim-methyl are lower than those for the alternatives, which could result in a reduction in exposure of the general public and workers to fungicides if Sovran® were used instead. In view of the above, the NYSDOH did not object to registration of Sovran® Fungicide in New York State if the issues related to groundwater/drinking water contamination potential are adequately addressed and mitigated as appropriate to protect public health.
ECOLOGICAL EFFECTS RISK ASSESSMENT:
The Sovran® Fungicide formulation is identical to Cygnus® Fungicide, a 50 % active ingredient water-dispersible granule. A description of kresoxim-methyl chemical characteristics and mode of action can be found in the Cygnus® registration letter, dated December 3, 1999.
The Department's runoff model (AQUALIFE) was employed to assess potential impacts to non-target organisms. All toxicity and fate values were taken from the data package submitted by BASF. An apple use scenario was modeled since the highest rate allowed for a single application, 0.2 pounds kresoxim-methyl/acre, is for pome fruits. Given kresoxim-methyl's average field dissipation half-life of one day and application intervals of seven to 21 days, multiple applications were not modeled. When modeling orchard applications, 60% of the runoff water is assumed to reach the model pond.
Avian and mammalian acute and chronic feeding exposures were modeled for the 0.2 pound kresoxim-methyl/acre application rate. Sovran® is practically non-toxic to both birds and mammals. With the allowed application rates, vegetation residue levels are several orders of magnitude below those at which toxicity could occur.
The AQUALIFE model predicted that kresoxim-methyl water concentration due to runoff following a single application at the highest allowed rate exceeded a number of marine invertebrate toxicity thresholds. The oyster acute NOEL is exceeded at the 3% runoff level in all water depths and in the one- and three-foot depths at 1.5% runoff. The mysid shrimp acute NOEL is exceeded at the one-foot depth at the 3% runoff rate.
The minor exposures noted above are unlikely to occur under field conditions. There is extensive label language warning of the potential for this product to contaminate surface waters via runoff. Even if the modeled water concentrations were achieved, it would likely be of little consequence to aquatic organisms given the very short degradation times for the parent compound.
The primary metabolite BF 490-1 is persistent, its aerobic soil half-life is 131 days. Mobility predictions based on its chemical characteristics and the results of lab studies have not been confirmed in the field dissipation studies submitted in support of this registration. BF 490-1 is expected to be very persistent in surface waters. No data is available on the toxicity of BF 490-1 to terrestrial organisms. Based on the low toxicity seen in studies with the parent compound, and the fact that kresoxim-methyl rapidly metabolizes to the degradate, it is likely that any toxic effects from the degradate would have been exhibited in studies conducted with the parent. Further, while the parent compound is highly toxic to freshwater fish and invertebrates, the degradate has been shown to be practically non-toxic to them. It is likely that BF 490-1 poses little risk to terrestrial organisms. Given the results of the freshwater organism testing, BF 490-1 is not likely to be toxic to marine fish or invertebrates on an acute basis. No data on the chronic toxicity of BF 490-1 to aquatic organisms has been submitted. It would seem advisable to examine this area given its potential for mobility and its expected persistence in aquatic habits.
In summary, kresoxim-methyl has very low avian and mammalian toxicity but is highly to very highly toxic to aquatic organisms. The parent compound degrades quickly via aerobic and anaerobic microbial metabolism and is not likely to persist long enough to be transported to surface waters. The primary degradate, BF 490-1, is persistent and has the chemical characteristics of compounds that are known to leach to groundwater or move offsite to surface waters. Limited toxicity testing with BF 490-1 shows it to be practically non-toxic to freshwater organisms on an acute basis. When used as labeled, Sovran® should not adversely impact fish or wildlife.
ENVIRONMENTAL FATE RISK ASSESSMENT:
The first kresoxim-methyl product (Cygnus® Fungicide) registered in New York State was labeled "Not for use in Nassau and Suffolk Counties." BASF is applying to use Sovran® in all of New York State, and on Long Island with an accompanying groundwater monitoring program.
Kresoxim-methyl has a low water solubility of 2 ppm. It is stable to hydrolysis at pH 5, has a half-life of 34 days at pH 7, and a half-life of seven hours at pH 9, increasing with alkalinity. Kresoxim-methyl photodegrades very slowly with a half-life of 37.2 days in water and 35.2 days on soil. Aerobic soil metabolism half-life is 0.9 days and aerobic aquatic metabolism half-life is 1.3 days. Anaerobic aquatic metabolism in a flooded soil system yielded a half-life of 1.1 days. Kresoxim-methyl was found to be very mobile in sand, loamy sand and clay soils with Kocs ranging from 320 to 567, with an average of 419.
The major degradate, BF 490-1, is more stable than the parent compound in aqueous media. It is more persistent than the parent compound in soil (aerobic half-life was 131 days) and aerobic aquatic metabolism half-life was greater than 100 days. BF 490-1 is highly mobile with Kocs of 43 in clay, 33 in loam and 69 in loamy sand (average 48). Mobility in alkaline soil is expected to be higher than in acid soil. BF 490-1 is highly water soluble at 3,661 ppm.
The Department's groundwater model (LEACHM) was run using Riverhead soil, a Koc of 541 for the parent and Koc of 20 for the degradate BF 490-1, a half-life of one day and an application rate of 0.8 lb kresoxim-methyl/acre/year. For the parent, the model projected one peak in year seven, the wet year, of much less than 1 ppb. For BF 490-1, an 80% degradation rate was modeled. The model projected three peaks; one in year six of about 0.08 ppb, one in year seven of 0.05 ppb, and a peak in year eight (due to wet year seven) of about 0.18 ppb.
Based on their environmental fate assessment (06/14/99), the USEPA's Environmental Fate and Effects Division (EFED) concluded that kresoxim-methyl is not likely to persist in surface waters because it degrades very rapidly in the aquatic system under aerobic and anaerobic conditions. Furthermore, if kresoxim-methyl reaches surface water with an alkaline pH, the dissipation of the parent would increase due to alkaline hydrolysis. The potential for BF 490-1 to reach surface waters after the application of kresoxim-methyl in the field is high, especially if a runoff-producing rain event occurs within several days to weeks after application. Surface water runoff will compete with movement to groundwater. Once BF 490-1 reaches surface waters, it is expected to be very persistent under either aerobic or anaerobic conditions.
The Sovran® product label bears the following advisories:
Surface Water Advisory: This chemical can contaminate surface water through spray drift. Under some conditions, it may also have a high potential for runoff into surface water (via both dissolution in runoff water and adsorption to eroding soil), for several days, post-application. These include poorly draining or wet soils with readily visible slopes towards adjacent surface waters, frequently flooded areas, areas over-laying extremely shallow ground water, areas with in-field canals or ditches that drain to surface water, areas not separated from adjacent surface waters with vegetated filter strips, and highly erodible soils cultivated using poor agricultural practices such as conventional tillage and down the slope plowing, and areas where an intense or sustained rainfall is forecasted to occur within 48 hours.
Ground Water Advisory: This chemical has properties and characteristics associated with chemicals detected in ground water. The use of this chemical in alkaline areas where soils are permeable, particularly where the water table is shallow, may result in ground water contamination.
Given its short half-life and the Sovran® product's low application rate, the parent kresoxim-methyl should not have an impact on ground or surface water. However, the degradate BF 490-1 is more mobile and more persistent than the parent, and the USEPA required both a ground and surface water advisory on the label. Based on this information, a ground water monitoring program should be implemented to support use of Sovran® on Long Island.
Environmental fate and expression data indicate that kresoxim-methyl and its BF 490-1 degradate have physical/chemical characteristics in common with those pesticides that are known to leach to groundwater or to move offsite to surface water. The potential for kresoxim-methyl and primarily the degradate BF 490-1 to impact vulnerable groundwater resources cannot be discounted. The sole source aquifers on Long Island, where permeable soils and shallow depth to groundwater are prevalent, are especially vulnerable to contamination. BASF has committed to a groundwater monitoring program in conjunction with the use of kresoxim-methyl on Long Island.
The Department hereby conditionally accepts Sovran® Fungicide (EPA Reg. No. 7969-154) for registration in New York State. Enclosed for your files are the Certificate of Pesticide Registration and New York State stamped-"ACCEPTED" labeling. As a condition of registration, BASF must conduct a groundwater monitoring program on Long Island in conjunction with the use of Sovran® Fungicide on grapes. The latest draft of a ground water monitoring program protocol titled "Ground Water Monitoring Of Kresoxim Methyl In Four Suffolk County, New York Vineyards" was submitted by BASF on February 28, 2000. BASF must provide this office, within 30 days of receipt of this letter, with three copies of a revised groundwater monitoring program protocol which incorporates the following:
Please contact Maureen P. Serafini, Chief of our Pesticide Product Registration Section, at (518) 457-7446, if you have any questions.
Stephen Hammond, P.E.
Division of Solid & Hazardous Materials
cc: w/enc. - N. Kim/D. Luttinger, NYS Dept. of Health
J. Leach/J. Kaplan, NYS Dept. of Health
R. Zimmerman/R. Mungari, NYS Dept. of Ag. & Markets
G. Good/W. Smith, Cornell PMEP
bcc: w/enc. - S. Hammond (2)
J. Colquhoun/T. Martin, DFW&MR
SPCS I, Reg. 1
PCS II's, Regions 2-7 &9
D. Rollins, Region 8
M. Radzevich (2)
BASF Corporation File
bcc: w/o enc. - T. Lynch