New York State Department of Environmental Conservation Division of Solid & Hazardous Materials th Bureau of Pesticides Management, 11 Floor 625 Broadway, Albany, New York 12233-7254 Phone: 518-402-8788 FAX: 518-402-9024 Website: www.dec.ny.gov E-Mail: ppr@gw.dec.state.ny.us Alexander B. Grannis Commissioner November 25, 2008 CERTIFIED MAIL RETURN RECEIPT REQUESTED Ms. Jill Sensibaugh Novozymes Biologicals, Inc. 5400 Corporate Circle Salem, Virginia 24153 Dear Ms. Sensibaugh: Re: Registration Decision for TAE-001 Technical Bioinsecticide (EPA Reg. No. 70127-7); Met 52 (EPA Reg. No. 70127-8); Tick Ex G (EPA Reg. No. 70127-9); and Tick Ex EC (EPA Reg. No. 70127-10) Containing the Active Ingredient Metarhizium Anisopliae Strain F52 (chemical code 029056) The New York State Department of Environmental Conservation (Department) has completed its technical review of the Novozymes Biologicals, Inc., application to register four products which contain Metarhizium anisopliae strain F52. The new active ingredient (NAI) product applications were received on July 16, 2007 and October 16, 2007. The applications and additional information were determined to be complete for technical review on May 5, 2008. The initial registration decision date was set for October 2, 2008. However, the Department had questions regarding the need for personal protective equipment (PPE) for labeled use of the product and Novozymes interest in marketing to the homeowner market. The original registration decision date was waived in order to review these questions with the registrant. The new registration decision date of December 2, 2008 was established after communication between the Department and the registrant regarding product application directions and PPE requirements on the end-use product labels were reviewed. There are three formulated products which are labeled for control of arthropods on outdoor residential and institutional turf and landscapes and one technical product for formulation into final use products. The Department has determined that this active ingredient and the labeled use of the formulated products, meet the current standards for protection of New York State resources. These four products have been accepted for registration in New York State. The Company has requested to withdraw the TAE-001 Technical Bioinsecticide (EPA Reg. No. 70127-7) until such time as they plan to package and sell this product. Pursuant to the review time frame specified by New York State ECL 33-0704.2, a registration decision date of December 2, 2008 was established. The Department has conducted the following technical reviews with regard to the registration of all four listed products containing the active ingredient Metarhizium anisopliae strain F52 for impacts to human health, nontarget organisms, and the environment. Review summaries are provided below.
Ms. Jill Sensibaugh 2. Human Health Assessment: The New York State Department of Health (DOH) reviewed the data submitted by Novozymes Biologicals, Inc., to register the pesticide products TAE-001 Technical Bio-Insecticide (EPA Reg. No. 70127-7), Met 52 (EPA Reg. No. 70127-8), Tick-Ex G (EPA Reg. No. 70127-9) and Tick-Ex EC (EPA Reg. No. 70127-10) in New York State. These pesticide products contain the new active ingredient Metarhizium anisopliae strain F52, which is a common soil microbe. Tick-EX G and Tick-EX EC are labeled for control of arthropods on residential and institutional turf and landscapes, and Met 52 is labeled for use on ornamentals. TAE-001 Technical Bio-Insecticide is labeled for manufacturing use whereas Met 52, Tick Ex-G and Tick-Ex EC are end-use formulations. The registrant was required to submit only limited study data on the toxicity and pathogenicity of Metarhizium anisopliae strain F52 for federal registration. The studies that were conducted consist of: acute oral, dermal, intra-tracheal and intra-peritoneal toxicity/pathogenicity; eye irritation; and dermal sensitization in laboratory animals. These studies were all conducted on the active ingredient and indicate that Metarhizium anisopliae strain F52 was neither toxic nor pathogenic. This material caused slight irritation in the eyes and skin of rabbits, but was not a dermal sensitizer (tested on guinea pigs). No acute exposure studies on the end-use products, and no subchronic, chronic/oncogenicity or reproductive/developmental toxicity studies are available for this active ingredient. The registrant indicates that Metarhizium anisopliae strain F52 has not been associated with any adverse effects in personnel involved in the development, manufacturing, testing or use of this material. A search of the scientific literature did not find any directly relevant toxicity/pathogenicity information on Metarhizium anisopliae strain F52 as related to pesticidal use. However, one study from the open literature investigated the allergenicity of Metarhizium anisopliae strain 1080 in mice. In this study, soluble factors from this microorganism were prepared and administered intra-tracheally as a challenge dose to sensitized mice (previously administered the antigen intra-peritoneally). Serum and bronchoalveolar lavage fluid obtained from the treated mice indicated that these mice exhibited immune and pulmonary inflammatory responses, suggesting that the crude Metarhizium anisopliae strain 1080 extract had some allergenic properties. Given the extraction process and the exposure protocol of this study, the relevance of these results to the use of the subject products is unclear. The dermal sensitization study on Metarhizium anisopliae strain F52 and the lack of identified adverse reactions among handlers of the products do not indicate similar allergenic potential. Given the labeled use of the Tick-Ex G and Tick-Ex EC products for tick control, which is a disease vector concern, several studies on the efficacy of Metarhizium anisopliae strain F52 against ticks were provided in the package. We also identified a published paper from the scientific literature that investigated the efficacy of Metarhizium anisopliae (strain unspecified) against ticks. Collectively, these studies evaluated the products or the fungal species under field and laboratory conditions. Some of these studies were conducted in New York State. Overall, these studies indicate that Metarhizium anisopliae, when applied to turf or the forest understory, can reduce populations of black-legged and Lone Star ticks. The pathogenic properties of Metarhizium anisopliae strain F52 against blacklegged and Lone Star ticks was confirmed in the laboratory where ticks exposed to the fungus were held and observed for evidence of infestation and mortality.
Ms. Jill Sensibaugh 3. The limited study data on Metarhizium anisopliae strain F52 indicates that this fungus is neither very toxic nor pathogenic in laboratory animals. It caused only slight eye and dermal irritation and was not a dermal sensitizer. This fungus has also not been associated with causing adverse effects in humans who have come into contact with the material during development, manufacturing or testing. Moreover, exposure of handlers to the subject end-use products should be mitigated by the label requirements for PPE (long-sleeved shirt, long pants, shoes plus socks, protective eyewear, waterproof gloves, and in the case of the two granular products (Met 52 and Tick-EX G)), a respirator. The labels require considerable PPE, and the use directions for the product are not very detailed. While these aspects of the products seem acceptable for commercial applicators, we had concerns that the products were not appropriate for the homeowner market. Consequently, we conducted a conference call with the registrant to better understand how these products would be marketed. During this call, the registrant indicated that the products are intended for commercial applicator use, and will be so marketed. The PPE requirements on the labels are conservative from the standpoint of minimizing worker risks and would not necessarily be indicated based on the limited toxicity/pathogenicity data available. However, we believe that these requirements represent good product stewardship and should be retained on the label. The registrant indicated during our conference call that they intend to market in the future a homeowner product for turf treatment of ticks and grubs. When they do, they anticipate that it will be a liquid formulation that will be marketed through a major retail chain or established formulator of homeowner products. The liquid formulation of such a product could diminish the need for applicators to use a respirator, as a liquid product would not be as likely to result in inhalation exposure during handling as would a dry formulation. The registrant also expects to expand the information on the label to better inform users about proper application methods and timing. The proposed product labeling is protective of applicators and does not pose a health concern to the general population. Nontarget Organism Assessment: The Department s Bureau of Habitat (BoH) reviewed the information submitted by Novozymes Biologicals, Inc., for the four insecticide products (TAE-001 Technical Bio-Insecticide, Met 52, Tick-EX G, and TICK-EX EC) with the active ingredient Metarhizium anisopliae Strain F52 for effects to non-target organisms. It appears that Tick-EX G and Tick-EX EC could prove to be efficacious products for controlling ticks that are primary vectors for lyme disease. As registered products, they would provide much more reasonable alternatives than the products that propose to treat ticks on deer or rodents. Since these products also kill grubs (Japanese beetle and June beetle larvae), their availability could help reduce the use of more toxic products registered for use on home lawns for insect pest control. Used as labeled, none of the product that use spores of the entomopathogenic fungus Metarhizium anisopliae are likely to be harmful to birds, mammals, aquatic organisms, plants, or most beneficial insects. It must be noted that these naturally occurring fungi assuredly have a broader host range than is represented by the target species listed on the label and the few nontarget insect species tested. Some beneficial insects would possibly be harmed by this product. For example, the EPA Biopesticides Registration Action Document for Metarhizium anisopliae Strain F52 reports that the insidious flower bug (Orius insidiosus), an aggressive
Ms. Jill Sensibaugh 4. predator of thrips and possibly some other pests, showed a high rate of susceptibility to M. Anisopliae. However, applications of general organophosphate, neonictinoid, or synthetic pyrethroid insecticides have a much greater potential of harming a broader scope of exposed, nontarget insects. Furthermore, these fungi-based products have the potential of selectively controlling ticks that are a major vector of diseases such as lyme disease. Many of the current lawn pesticides used to control grubs are also highly toxic to birds and mammals, which the fungi-based products are not. Thus, even though this product will not be harmless to all nontarget insects that are exposed, in balance it is likely to have significant ecological and human health benefits. Environmental Fate Assessment: The active ingredient Metarhizium anisopliae Strain F52, is ubiquitous in nature and has been evaluated by the USEPA as a biopesticide. Environmental fate data were not required for federal review and consequently, there is no impact to the groundwater to be assessed. Impact to environmental resources in New York State are expected to be minimal due to the lack of exposure, low toxicity, use pattern and application methods. Registration Summary: Enclosed for your record are copies of the stamped accepted labeling and the Certificate of Registration for Met 52 (EPA Reg. No. 70127-8); Tick Ex G (EPA Reg. No. 70127-9); and Tick Ex EC (EPA Reg. No. 70127-10). At such time as Novozymes Biologicals, Inc. chooses to apply for the registration of TAE-001 Technical Bioinsecticide (EPA Reg. No. 70127-7) a new routine product application and fee must be submitted to this Department. Please note that a proposal by Novozymes Biologicals, Inc., or any other registrant, to register a product that contains Metarhizium anisopliae Strain F52 for any 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 (September 2005). 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 our Pesticide Product Registration Section, at (518) 402-8768. Sincerely, Maureen P. Serafini Enclosures Maureen P. Serafini Director Bureau of Pesticides Management ecc: w/enc. - R. Mungari - NYS Dept. of Ag. & Markets A. Grey/E. Horn - NYS Dept. of Health W. Smith - Cornell University, PSUR