Mr. John Abbott
Syngenta Crop Protection, Inc.
P.O. Box 18300
Greenboro, NC 27419-8300
Dear Mr. Abbott:
Re: Registration of Actigard 50WG (EPA Reg. No. 100-922) containing the New Active Ingredient: Acibenzolar-S-Methyl.
The New York State Department of Environmental Conservation (the Department) has completed its technical review of your application materials submitted in support of the registration of Actigard 50WG (EPA Reg. No. 100-922). The Department is registering Actigard 50WG (EPA Reg. No. 100-922) for the preventive control of downy mildew in leafy vegetables, bacterial leaf spots on tomatoes, and blue mold on tobacco.
The Department has identified from the United States Environmental Protection Agency (USEPA) documentation and confirmed with you, that the manufacturing process for this product is expected to change in order to remove an impurity. The USEPA Health Effects Division has determined that one of the impurities has produced positive results in a gene mutation assay and that they may be requesting additional data. The USEPA is currently reviewing the changes proposed for the manufacture of the Actigard product. The Department may require a "Major Change in Label" review based on USEPA recommendations.
The active ingredient, acibenzolar-s-methyl (1,2,3-benzothiadiazole-7-thiocarboxylic acid-s-methyl-ester) induces in plants, a natural defense reaction that enhances the plant's physiological ability to increase plant health and to ward off disease. Because of its unique mode of action, the International Standards Organization has created a new category for this active ingredient called Plant Activator.
The Actigard 50WG product is applied in a foliar application either alone or tank mixed with other registered products with curative activity, as part of a resistance management program. Actigard 50WG contains 50% by weight of the active ingredient acibenzolar-s-methyl, the maximum annual application is four ounces per acre per year. Individual applications can be made at a rate of no more than six applications of 1/3 to 3/4 oz. per acre. This maximum application rate is specific to tomato crops, applications to spinach and tobacco require less product per acre per season. The focus of the technical reviews were for the use of this product on tomato crops in New York State and the subsequent health effects and impact to environmental resources.
The Application was received by the Department on September 8, 2000
and was deemed incomplete for purposes of technical review on November 1, 2000.
The application required several USEPA documents including Data Evaluation
Records (DERs) and an Environmental Fate and Effects Division review of the
active ingredient in order for the Application to be considered complete.
The missing information was submitted by the Applicant on March 8, 2001.
The Application and additional data were reviewed and a completeness
determination was issued on April 17, 2001. Pursuant to the review time
frame specified in ECL §33-0704.2, a registration decision date of September
14, 2001 was established. The Department conducted the following technical reviews with regard to the registration of Actigard 50WG, for impacts to human health, non-target organisms, and the environment. The human health technical review required more information to satisfy New York State requirements. Information was received from Syngenta Crop Protection, Inc. by this Department on September 6, 2001.
Human Health Review:
Both Actigard 50WG and the active ingredient acibenzolar-s-methyl were reviewed for impacts to human health. Neither acibenzolar-s-methyl nor Actigard 50 WG Plant Activator were very toxic in acute oral, dermal, or inhalation exposure studies in laboratory animals, nor were they very irritating to the eyes or skin (tested on rabbits). Although the active ingredient was a skin sensitizer, the formulated product did not show skin sensitizing properties (tested on guinea pigs).
Neither acibenzolar-s-methyl nor the Actigard product was very toxic following acute exposure in laboratory animal studies. Acibenzolar-s-methyl also was not very toxic following chronic exposures and did not cause oncogenic effects. This chemical, however, caused developmental toxicity after ingestion in pregnant rats and rabbits. In rats, developmental effects were noted at dose levels below those that caused maternal toxicity. The USEPA conducted a number of analyses to evaluate the health risks from exposures to acibenzolar-s-methyl, giving special consideration to infants, children, women of childbearing age, and agricultural workers. The results of these analyses indicate that such exposure will not exceed USEPA levels of concern. However, the Department requested and received further information on the various assumptions to derive the acute dietary exposure estimate for females ages 13 to 50 years which is very close to the USEPA level of concern. The information provided and further assessments by staff have satisfied the Department that the current use pattern for Actigard 50 WG will not present a significant risk to human health when used in accordance with label directions. However, a major change in labeled use pattern such as the addition of other crops would possibly exceed the limits of acceptable exposure for this group.
Acibenzolar-s-methyl did not cause oncogenic effects in either rat or mouse feeding studies. It was also negative in a number of genotoxicity tests except for one study which presented suggestive evidence of chromosomal aberrations. The USEPA classified acibenzolar-s-methyl as "not likely to be carcinogenic to humans."
There are no chemical specific federal or State drinking water/groundwater standards for acibenzolar-s-methyl or it's degradates. Based on their chemical structure, acibenzolar-s-methyl and it's degradates fall under the 50 microgram 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 &g/L. If one uses the cPAD derived for females ages 13 to 50 years (0.0033 mg/kg/day) and procedures for deriving ambient water standards and guidelines based on non-oncogenic effects (6NYCRR Part 702.5), a value of 23 &g/L can be calculated for acibenzolar-s-methyl.
Non-Target Organism Review:
Technical acibenzolar-s-methyl has a water solubility of 7.7 mg/L. It has a low vapor pressure, 3.5x10-6 mm Hg, volatilization will not contribute significantly to dissipation. With a relatively low octanol/water partition coefficient, KOW , of 1259 it should not bioaccumulate significantly. A bluegill sunfish accumulation study yielded bioconcentration factors for whole fish, viscera, and fillets of 118x, 199x, and 48x respectively. Greater than 90% of accumulated acibenzolar-s-methyl was depurated within 14 days of exposure cessation.
TOXICITY AND ENVIRONMENTAL FATE:
Acibenzolar-s-methyl is practically non-toxic to birds or mammals on both an acute and chronic basis. It is moderately to highly toxic to freshwater fish, is moderately toxic to freshwater invertebrates and estuarine fish, and is highly toxic to estuarine/marine invertebrates. Acibenzolar-s-methyl is also toxic to aquatic plants.
Acibenzolar-s-methyl dissipates fairly rapidly in the environment via both biotic and abiotic pathways. Terrestrial field dissipation studies yielded half-lives (T1/2's) that ranged from 7 to 27 days. It is stable to hydrolysis at environmentally relevant pH's. At pH 7 the T1/2 is 23 weeks. Its laboratory aqueous photolysis T1/2 is 36 minutes. No acceptable soil photolysis data was submitted. A supplemental aerobic soil metabolism study yielded a T1/2 of approximately 5 hours. The study was classified as supplemental by the USEPA because the European soil used was not adequately compared to those of the continental United States. A supplemental aerobic aquatic metabolism study, conducted with both Rhine river water and sediment, and pond (Judentiech, Rheinfelden CH) water and sediment, yielded T1/2's of 19.7 hours and 15.1 hours respectively. As with the aerobic soil study, the aquatic study was classified supplemental because the Rhine river sediments were not adequately compared to United States river sediments. The DT90, time to 90% dissipation, in the river sediment/water system was approximately 65 hours, in the pond sediment/water system it was approximately 50 hours.
The U.S. EPA Health Effects Division (HED) identified acibenzolar-s-methyl metabolites CGA-210007, CGA-324041, and CGA-323060 as well as the parent compound as residues of concern for risk assessment. The only metabolite detected in terrestrial field dissipation studies was CGA-210007. Field half-lives for CGA-210007 in
California tomato and bare soil plots, and N. Carolina bare soil plots were calculated to be 45, 59 and 7 days respectively. CGA-210007 is more soluble (225ppm) than the parent compound and is expected to be more mobile in soil. Aquatic organism acute toxicity tests were conducted with CGA-210007, it is practically non-toxic to rainbow trout, daphnia, and the green algae selenastrum capricornutum.
No terrestrial or aquatic toxicity thresholds were exceeded with the exception of the rainbow trout NOEL when the seasonal maximum rate was applied directly to the surface of the model pond.
No adverse effects to fish or wildlife resources are likely
to occur when Actigard is used as labeled. It should be noted however that
USEPA documents submitted with this data package state that a new manufacturing
process is planned for the active ingredient and that the new process results
in additional impurities that were not found in the product reviewed here. The
USEPA HED has indicated that one of the impurities has produced positive
results in a gene mutation assay and that they may be requesting additional data.
Environmental Fate Review:
Running LEACHM on Riverhead soil using a Koc of 1447 for the parent and a Koc of 561 for the degradate (83%), a half-life of 16 days (a field dissipation half-life because the aerobic study was unacceptable) and an application rate of 4 oz ai/acre/year (maximum use rate), the model projected no leaching of the parent or the degradate. In summary, the labeled use of this product would present a low application rate, fairly short half-life and moderate Kocs, it does not appear that the use of this product as labeled will impact groundwater.
Enclosed for your record is a copy of the stamped accepted label and the Certificate of Registration for Actigard 50WG (EPA Reg. No. 100-922). Please note that a proposal by Syngenta Crop Protection, Inc. or any other registrant, to register a product that contains acibenzolar-s-methyl, and whose labeled uses are likely to increase the potential for significant impact to humans, non-target 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 contact our Pesticide Product Registration Section, at (518) 402-8768 if you have any questions.
Bureau of Pesticides Management
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