November 9, Via UPS (Co. No ) Mr. Keith Pitts Marrone Bio Innovations 2121 Second Street, Suite B-107 Davis, CA Dear Mr.

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1 New York State Department of Environmental Conservation Division of Materials Management Bureau of Pest Management Product Registration & Pest Management Alternatives Section 625 Broadway, Albany, New York Phone: (518) Fax: (518) Website: Joe Martens Commissioner November 9, 2012 Via UPS (Co. No ) Mr. Keith Pitts Marrone Bio Innovations 2121 Second Street, Suite B-107 Davis, CA Dear Mr. Pitts: Re: Registration of the New Active Ingredient Pseudomonas fluorescens Strain CL145A Cells as Contained in Zequanox (EPA Reg. No ) (Active Ingredient Code ) The New York State Department of Environmental Conservation (Department) has evaluated your application, received May 15, 2012, in support of the registration of the abovereferenced pesticide product. Zequanox contains 50% of the active ingredient Pseudomonas fluorescens strain CL145A cells and is formulated as a wettable powder. It is labeled for control of quagga and zebra mussels in enclosed, semi-enclosed and other confined static or flowing water infrastructures. Zequanox may not be used in open water such as ponds, lakes, reservoirs, rivers, and streams. It is to be applied using a chemical metering pump directly into the treatment area. The maximum application rate is oz of active ingredient per gallon of water for up to 24 hours total per month. Pseudomonas fluorescens strain CL145A is a naturally occurring bacterium originally isolated from river mud in the northeastern United States and is commonly found in soil, on plant surfaces, and in water. It is one of the more common bacterial species used to control diseases on the leaf surfaces of plants. The application package was deemed complete for purposes of technical review on July 16, Pursuant to the review time frame specified in Environmental Conservation Law , a registration decision date of December 13, 2012 was established.

2 Mr. Keith Pitts 2. Technical reviews of the proposed uses included on the Zequanox label have been performed by the Department and the New York State Department of Health. These reviews encompassed the expected impacts of labeled use of the subject product with respect to human health and ecological effects. The technical reviews are shown below. HUMAN HEALTH ASSESSMENT: The following assessment was prepared by staff within the Bureau of Toxic Substance Assessment at the New York State Department of Health. The U.S. Environmental Protection Agency (U.S. EPA) required limited toxicity testing on the active ingredient and formulated product for federal registration. In an acute pulmonary toxicity/pathogenicity study in rats, P. fluorescens strain CL145A was not toxic, infective or pathogenic at 3.4 x 10 8 colony forming units (cfu) per animal. High mortality was observed in an acute (intravenous) injection toxicity/pathogenicity study in rats, but the cause (i.e., the bacteria itself or a released toxin) was not established. The U.S. EPA considered this study supplemental for registration and concluded that even though the cause of the mortality is unclear, there is adequate information to perform a risk assessment based on results from other toxicological studies which demonstrated low mortality with freshly prepared test substance and a lack of toxicity with autoclaved culture. This bacterium was neither acutely toxic via oral, dermal, or inhalation routes of exposure, nor an eye nor skin irritant (tested on rabbits). Acute toxicity testing on the formulated product was waived by the U.S. EPA because of: (1) P. fluorescens strain CL145A s natural occurrence in soil, in water, and on the surface and roots of a variety of plant types (including those of raw foods); (2) pseudomonads being considered a benign part of the regular human diet; and (3) the inert ingredients being present in diluted form and not expected to be of toxicological concern. A search of the toxicological literature did not find any additional significant information on P. fluorescens strain CL145A. The U.S. EPA waived the requirements for subchronic, chronic, developmental, reproductive toxicity, genotoxicity and oncogenicity studies for federal registration of products containing P. fluorescens strain CL145A. The U.S. EPA additionally exempted this active ingredient from tolerance requirements (Federal Register 76 (No. 164): 52,871 52,875; August 24, 2011) due to its lack of toxicity, infectivity and/or pathogencity. The Biopesticides Registration Action Document (BRAD) for this bacterium states that no hypersensitivity incidents, including immediate or delayed reactions of humans were reported during research, development, or testing of these products. However, due to the potential for allergic sensitization, a dust/mist filtering respirator is required for handlers that may be exposed to the active ingredient for prolonged periods or numerous times. Accordingly, the product label carries the following warning statement: Repeated exposure to high concentrations of microbial proteins can cause allergic sensitization. The limited toxicity data required to support the federal registration of this product indicate that it is not very toxic following acute exposures. The active ingredient P. fluorescens strain CL145A also appears to lack pathogenicity and infectivity to animals, and has not been associated with causing adverse effects in humans. In addition, the labeled use of the Zequanox

3 Mr. Keith Pitts 3. product in enclosed, semi-enclosed and other confined static or flowing water infrastructures should result in negligible exposure to the general public. Given the above, the New York State Department of Health does not object to the registration of Zequanox in New York State. ECOLOGICAL EFFECTS ASSESSMENT: The Department s Bureau of Habitat evaluated the proposed use of Pseudomonas fluorescens strain CL145A cells as contained in Zequanox. Shown below is the assessment. Background: Zequanox is a highly specific toxicant to only zebra and quagga mussels. When live or killed Pseudomonas fluorescens strain CL145A cells are applied to water structures infested with zebra and/or quagga mussels, the mussels ingest and filter the material, which then degrades the epithelial lining of digestive tubules in their digestive glands and kills them. This toxic effect appears to be limited to mussels of the Genus Dreissena, and similar toxicity is not observed with fish, aquatic invertebrates or other freshwater unionid mussels (see section 2, Toxicity). Zequanox is labeled for three types of treatments: A. Rehabilitation Level Treatment is designed for adult zebra and quagga mussel control. It is applied at a maximum application rate of 200 mg AI/L of treated water. The water must be continuously injected in flowing water systems for 6 to 12 hours, or held in non-flowing, static water systems for hours. Rehabilitation treatments are typically done once per year and cannot be done more than twice per year. B. Settlement Maintenance Level Treatment is an on-going, lower dose treatment conducted during the zebra mussel spawning season that prevents juvenile mussels from settling and growing to the adult stage. The maximum application rate is 50 mg AI/L for up to 12 hours per treatment, and can be done no more than two times per month per treatment site. C. Veliger Treatment is a low dose treatment conducted during the mussel spawning season to control the swimming and floating mussel life stages within a defined static volume or flowing water. These treatments are typically performed where infested water is being transferred from one location to another, to prevent the spread of invasive mussels into non-mussel infested water. The maximum application rate is 50 mg AI/L for up to 12 hours per treatment, and is limited to one treatment per specific volume of treated water being transferred. Upon completion of a treatment, Zequanox can be discharged to receiving waters, but the discharge must be regulated so that the concentration of active ingredient in the receiving water does not exceed 100 mg AI/L. Furthermore, the label requires that discharges of water treated with Zequanox must be in accordance with the requirements of a State Pollutant Discharge Elimination System (SPDES) permit.

4 Mr. Keith Pitts 4. Toxicity: Toxicity testing has demonstrated that Pseudomonas fluorescens Strain CL145A exhibits very little toxicity to organisms other than zebra mussels. Acceptable acute toxicity data for Pseudomonas fluorescens strain CL145A demonstrated that it is either Toxicity Category III (slightly toxic) or Toxicity Category IV (practically nontoxic), while an acceptable acute pulmonary toxicity/pathogenicity study indicated that Pseudomonas fluorescens Strain CL145A is not toxic, infective, and/or pathogenic. Specific toxicity tests conducted with Pseudomonas fluorescens Strain CL145A are detailed below in Table 1. Table 1. Summary of ecotoxicological testing with Pseudomonas fluorescens Strain CL145A. Organism Test Result Comment Rat Acute oral, gavage, single dose of technical grade material LD 50 > 5,000 mg/kg bw NOEC = 5,000 mg/kg bw Equivalent to >2.35x10 10 CFU/Kg Mallard duck Rainbow trout, Oncorhynchus mykiss Acute oral, gavage, single dose of technical grade material 96 hour acute (static LD 50 > 2,000 mg/kg bw NOEC = 2,000 mg/kg bw LC 50 = mg AI/L NOEC = 25 mg/l Chinook salmon 96 hour acute (static LC 50 = mg AI/L NOEC = 90 mg/l Common carp 96 hour acute (static) LC 50 = mg AI/L NOEC = 250 mg/l Bluegill 96 hour acute (static LC 50 = mg AI/L NOEC = 90 mg/l Fathead minnow 96 hour acute (static LC 50 = mg AI/L NOEC = 100 mg/l Sacramento splittail 96 hour acute (static LC 50 = mg AI/L (Cyprindae) NOEC = 50 mg/l Daphnia magna 48 hour acute (static) LC 50 > 100 mg AI/L NOEC = 100 mg/l Green algae 72 hour acute (static) EC 50 = mg AI/L Selenastrum NOEC = 50 mg/l capricornutum 14 day limit dose Author hypothesized that toxicity might have resulted from the high turbidity caused by the test material as opposed to a toxic response to the test material Oncorhynchus tshawytscha Cyprinus carpio Lepomis macrochirus Pimphales promelas Pogonichithys macrolepidotus Endpoint = immobilization Endpoint cell density. Test graded as Supplemental

5 Mr. Keith Pitts 5. Organism Test Result Comment Hyalella azteca 10 day whole sediment IC 50 > 100 mg AI/L NOEC = 100 mg/l 76% survival at 100 mg/l. Test graded as Supplemental Exposure: The environmental fate of killed Pseudomonas fluorescens Strain CL145A cells was not formally reviewed. However, the registrant documented that in oxygenated water, Zequanox decays naturally over a 24 hour period. The degradation of Zequanox was tested/confirmed by testing water in jars in which Zequanox had been added 24 hours prior to exposing zebra mussels. The aged Zequanox had no toxic effect on the zebra mussels, confirming the degradation of the Zequanox active ingredient. Only one application scenario for Zequanox includes an application rate greater than 50 mg/l, which is the rehabilitation treatment. In this scenario, the confined water system is treated at a maximum concentration of 200 mg AI/L. In static systems, the water must be held for hours, and during that time it will be 50 75% degraded. Zequanox can be applied to flowing systems at 200 mg AI/L for 6-12 hours, but the label requires that discharges cannot contain more than 100 mg AI/L, so mixing with untreated water must occur in such a system prior to discharge. The LC 50 s of all but two tested organisms exceeded 100 mg/l; only the LC 50 s for the rainbow trout and green algae were lower. Dilution from the receiving water will further reduce the Zequanox AI concentration in the effluent, so it is unlikely to persist in a receiving water for very long. Furthermore, the registrant contends that rainbow trout mortality was more likely caused by high turbidity as opposed to toxicity. In the test, rainbow trout were exposed continuously to high turbidity for 96 hours with no opportunity for avoidance. This is eight times longer than discharges of Zequanox-treated water are allowed, and in the wild, rainbow trout would be able to avoid the turbidity plume. Modeling studies and field trials of Zequanox have shown that when used in the types of facilities most likely to be impacted by zebra mussels (i.e., power plants, hydroelectric facilities), discharges of Zequanox-treated water dissipated very quickly over short distances downstream from treated facilities. Risk Assessment: When used as labeled, Zequanox is unlikely to have any adverse impacts to aquatic ecosystems. It exhibits very low toxicity to aquatic organisms other than zebra mussels, and degrades rapidly, on the order of 100% degradation in 24 hours. Only one treatment application rate exceeds the typical LC 50 s for most aquatic organisms, but the label restrictions limit the discharge of the treated effluent to half of the highest application rate allowed. That concentration will be rapidly diminished by dilution with the receiving water, and the duration of discharges can only last for 1/4 to 1/2 of the duration of the toxicity tests. No adverse impacts from the labeled use of Zequanox are anticipated. Therefore, Bureau of Habitat staff does not object to registration of Zequanox in New York State.

6 Mr. Keith Pitts 6. REGISTRATION DECISION The Department concludes that the use of Zequanox should not have an adverse effect on human health or the ecology of New York State. Therefore, the Department hereby registers Zequanox (EPA Reg. No ) in New York State. Enclosed for your record are copies of the Certificate of Pesticide Registration and stamped Accepted for Registration labels. Please note that a proposal by Marrone Bio Innovations or any other registrant to register a product that contains Pseudomonas fluorescens strain CL145A cells, and whose labeled uses are likely to increase the potential for significant impact on humans, nontarget organisms, or the environment, would constitute a major change in labeling. 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 (April 2009). Such information, as well as forms, can be accessed at our website as listed in our letterhead. letter. Please contact Shaun Peterson, at , if you have any questions regarding this Sincerely, Scott Menrath Enclosures Scott Menrath, P.E. Director Bureau of Pest Management