September 21, VIA E_MAIL (Co. No )

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1 (518) September 21, 2017 VIA E_MAIL (Co. No ) Ms. Nora Mealy Marrone Bio Innovations c/o Technology Sciences Group Inc. 712 Fifth Street, Suite A Davis, California Dear Ms. Mealy: Re: Registration of the Major Change in Labeled Use of Heat-Killed Burkholderia spp. Strain A396 Cells and Spent Fermentation Media (Chemical Code: ) as Contained in Venerate XC (EPA Reg. No ) The New York State Department of Environmental Conservation (Department) has evaluated your application, received August 22, 2017, and all additional information received to date in support of the registration of this active ingredient and formulated product. The Venerate XC product was previously reviewed and subsequently denied registration as communicated in our letter dated December 11, 2015 in which concerns were raised for potential negative impacts to aquatic, plant, and insect species from aerial and foliar application of the product. The Department then conducted an abbreviated assessment of the Majestene formulated product (EPA Reg. No ) labeling and found the limited methods of application (soil drench, chemigation (drip, trickle, or sprinkler irrigation) and as an in-furrow spray, T-band or soil injection) would substantially reduce exposure for these non-target organisms. The Department subsequently registered Majestene on January 27, Majestene and Venerate XC are alternative brand names for the primary product named MBI-206 EP. The product contains 94.46% of the active ingredient heat-killed Burkholderia spp. strain A396 cells and spent fermentation media (also known as MBI- 206) and is formulated as a liquid solution. The formulated product is defined as a microbial biopesticide and labeled to control insect pests on a variety of agricultural crops. The application directions for each product label were evaluated based on the previous technical reviews performed by the Department s Division of Fish & Wildlife s Bureau of Habitat (BOH) and the New York State Department of Health (NYSDOH). These reviews encompassed the expected impacts of labeled use of the Majestene and

2 Ms. Nora Mealy 2. Venerate XC products with respect to human health and ecological effects. The full technical reviews from the previous application to register Venerate XC are provided in the Appendix. However, the determination to register the updated Venerate XC product labeling is found below and responds to the concerns raised in these assessments. Marrone Bio Innovations applied for and received stamped Accepted labeling from the U.S. EPA dated January 25, 2017 which, among other updates, added mitigative language to address concerns listed below that were raised during this Department s previous review: The Human Health Assessment provided by the NYSDOH concluded that a statement about the use of eye protection should be included in the list of required personal protective equipment (PPE) for applicators and other handlers as both the Majestene and Venerate XC product labeling require eye protection as stated in the Precautionary Statements. The Ecological Effects Assessment provided by BOH concluded that the information provided for review was not sufficient to adequately describe the risks to non-target resources. The Department recommended that an aerial application prohibition and a 100-foot buffer between surface water and the site of application would be protective of aquatic organisms. Review of label language that directs the applicator to reduce spray drift by not conducting applications when weather conditions would increase spray drift and to use methods and apparatus to minimize spray drift is found in various text throughout the Venerate XC label as well as an in-depth review found under the section titled: Aerial Application and Drift Reduction Advisory Information. The label is explicit that spray drift is to be minimized to protect beneficial insects, bees and pollinators. Spray drift reduction practices and the New York State aerial prohibition will further limit spray drift away from the target area thereby reducing potential impacts to non-target insects and plants. The Department hereby accepts Venerate XC (EPA Reg. No ) for registration as labeled in New York State. Enclosed for your records, is a copy of the New York State stamped Accepted for Registration label and New York State Certificate of Pesticide Registration for Venerate XC Bioinsecticide (EPA Reg. No ). Please note that a proposal by Marrone Bio Innovations or any other registrant, to register a product that contains heat-killed Burkholderia spp. strain A396 cells and spent fermentation media, and whose labeled uses or type of application method, are likely to increase the potential for significant impact to humans, non-target organisms, or the environment, would constitute a major change in labeled use pattern. Such an application must be accompanied by a new application fee and meet the requirements for major change in labeling applications as listed on our website:

3 Ms. Nora Mealy 3. Please also note that due to the concerns identified by our Bureau of Habitat staff, any additional products submitted for registration in New York State must contain the following language in order to be protective of aquatic organisms and non-target resources: In New York State, aerial application is prohibited In New York State, application is prohibited within 100 feet of any surface water Registration of products without this language will require the submission of additional supporting information that provides a more complete profile of the toxicity and fate of the active ingredient, heat-killed Burkholderia spp. strain A396 cells and spent fermentation media as detailed in the Addendum Ecological Effects Assessment. Please contact Paula McBath of our Pesticide Product Registration Section, at (518) , if you have any questions regarding this letter. Sincerely, /s/ Scott Menrath, P.E. Director Bureau of Pest Management

4 Ms. Nora Mealy 4. HUMAN HEALTH ASSESSMENT: APPENDIX The following technical review was produced by staff within the Bureau of Toxic Substance Assessment at the New York State Department of Health (NYSDOH): Toxicity Review The U.S. Environmental Protection Agency (U.S. EPA) required limited data for federal registration of heat-killed Burkholderia spp. strain A396 cells and spent fermentation media. Neither the active ingredient nor the formulated product Venerate XC were very toxic in acute oral, dermal or inhalation exposure studies in laboratory animals or irritating to the skin (tested on rabbits). In addition, neither caused skin sensitization (tested on guinea pigs). Heat-killed Burkholderia spp. strain A396 cells and spent fermentation media did cause moderate eye irritation (tested on rabbits), however, Venerate XC was not irritating to the eyes. The U.S. EPA waived the requirements for acute oral, pulmonary and injection pathogenicity studies because the active ingredient does not contain live Burkholderia spp. strain A396 cells. No further toxicity studies were required for federal registration of Venerate XC. The U.S. EPA concluded that this active ingredient poses no dietary risk to humans and granted a tolerance exemption for residues in or on all agricultural commodities (Federal Register 79(55); ; March 21, 2014). DOH staff s search of the toxicological literature found no additional data on the toxicity or pathogenicity of heat-killed Burkholderia spp. strain A396 cells spent fermentation media. Summary/Recommendation The available information on the toxicity of heat-killed Burkholderia spp. strain A396 cells and spent fermentation media indicates that the potential for significant risks to public health via dietary exposure is minimal. Occupational risks are also expected to be minimal as the U.S. EPA did not identify acute dermal or inhalation endpoints from the toxicity database. While no toxicity endpoints were identified, the U.S. EPA did note that repeated exposure to high concentrations of microbial proteins can cause allergic sensitization and required on the label that pesticide handlers wear personal protective equipment (long-sleeved shirt and long pants, waterproof gloves, shoes plus socks, and a dust/mist filtering respirator). In addition to these personal protective equipment requirements, the Venerate XC label also contains the precautionary statement causes moderate eye irritation wear goggles or safety glasses. Use of eye protection is found under the Hazards to Humans and Domestic Animals heading of the label, however, it is not included in the required personal protective equipment list. Given the above, DOH staff do not object to registration of Venerate XC on the basis of impacts to human health. However, DOH staff believe that a statement about the use of eye protection should also be included in the list of required personal protective equipment for applicators and other handlers.

5 Ms. Nora Mealy 5. ECOLOGICAL EFFECTS ASSESSMENT: The following is a combination of the original and follow-up technical review produced by the Department s staff within the Bureau of Habitat (BOH): Product Background Venerate XC Bioinsecticide is labeled for control or suppression of numerous foliar feeding insect pests. Insects controlled are all caterpillar larvae, primarily lepidopteran. Those listed as suppressed include aphids, whiteflies, plant sucking mites, stink bugs, and thrips. The label includes directions for use on 29 different crops or crop groups. Those grown in New York State (NYS) include: asparagus, bulb vegetables, bush berries, cane berries, cereal grains, cranberry, cole crops, corn (all), cucurbit vegetables, fruiting vegetables, grapes, herbs, spices and mints, leafy vegetables, oil crops (canola, safflower, sunflower), pome fruit, potatoes (and tuberous and corm vegetables), root vegetables, stone fruits, strawberry, and tree nuts. This list of potential use sites includes many of the major agricultural crops of NYS. According to the 2012 U.S.D.A. Census of Agriculture the above crops occupied roughly 1,498,885 acres of NYS land in Venerate XC may be applied using ground or aerial spray equipment. The label directions for all listed crops are the same. Applications of 1 to 8 quarts Venerate XC per acre are made using water as the carrier. For row crops the label recommends a minimum of 10 gallons of finished spray for ground applications and 5 gallons per acre by air. In orchard or tree crops, application to runoff is recommended for dilute sprays and uniform coverage for more concentrated sprays when using ground equipment. In orchards, 10 or more gallons per acre are used by aerial application. Reapplication intervals are 3-10 days depending on pest pressure. No upper application limits are stated. The Venerate XC label lists the active ingredient as Heat-killed Burkholderia spp. strain A396 cells and spent fermentation media (also known as MBI-206). The bacterium is identified in the submitted data package as Burkholderia cenocepacia. MBI-206 makes up 94.46% of the product by weight. The 1 quart per acre application rate equals 1.98 pounds of this active ingredient per acre (lbs ai/a) and 8 quart per acre equals roughly lbs ai/a. The active ingredient originally consisted of viable cells and spent fermentation media but concerns over pathogenic potential of this bacterial strain prompted the applicant, Marrone Bio Innovations Inc. (MBI), to add a heat-kill step to its production process. The ai is heated to 60 O C for at least 1 hour after fermentation is completed. Additionally, the End Use formulation contains 0.67% 1- hexanol as a co-solvent to degrade cellular membranes and inactivate any cells which may have survived the heating process. The label describes the Venerate XC mode of action as enzymatic degradation of exoskeletal structures and interference with the molting process leading to mortality through contact and/or ingestion. The 6 metabolites listed in Table 1 are the enzymatic degradation products. However, these metabolites are not clearly identified for MBI-206 in the submitted materials. Additionally, the amounts of each of these compounds in the active ingredient are not stated. The following table is reproduced from an U.S. EPA (EPA) Data Evaluation Record (DER) of a Product Identity information submission by MBI.

6 Ms. Nora Mealy 6. Table 1. Metabolites produced by Burkholderia spp. Strain A396 Templazole Metabolite FR FR A Molecular Wt. Templazole B Templamide A Templamide B Formula C27 H41 N C24 H36 N4 C17 H18 C15 H18 N2 C28 H45 N O9 O6 S2 N2 O3 O2 O10 CAS No NOT NOT NOT PROVIDED PROVIDED PROVIDED LD 50 Mouse IP Mouse IP 6.4 NOT NOT NOT 0.32 mg/kg mg/kg PROVIDED PROVIDED PROVIDED Herbicide X X X X X X Insecticide X X X X Nematicide X X X Fungicide X X X Bactericide X Drug X X C28 H43 N O9 NOT PROVIDED NOT PROVIDED In the DER, templazole A and B are described as resembling phenylurea herbicides and templamide A and B as mysin antibiotics. As a condition of registration, the EPA has required MBI to submit, within 1 year of the Notice of Registration date, information/studies on the identities and amounts of the bioactive metabolites produced during the manufacture of MBI The studies were required to be submitted to EPA by February MBI-206 is a complex biological mixture of cellular remains, bacterial secondary metabolites and/or toxins, and spent fermentation media. No specific compound or compounds have been identified as having the described mode of action. The only physical or chemical properties reported for MBI-206 is its mass of g/ml and a ph of Toxicity The Burkholderia spp. strain A396 active ingredient is practically nontoxic to all vertebrate test species for which study results were submitted. It is slightly toxic to Daphnia. No toxicity study results were submitted for algae or aquatic macrophytes. DERs were submitted for 12 separate toxicity tests, which were conducted with a range of terrestrial non-target insects. All of these tests were classified variously as either invalid, incomplete, or unacceptable. The first 3 studies were conducted with the original non-killed formulation. EPA reviewers gave these 3 tests A partial list of reasons for their classifications including: test results were inconclusive, not conducted at maximum hazard concentration, and Agency (EPA) cannot determine the toxicity of test item. The remaining 9 studies were required after the change in formulation. The primary factors resulting in an invalid result were the method of exposure and study duration. The formulation was sprayed on tomato plants, allowed to dry, then the test insects were introduced to a containment chamber with the tomato plants. The test chambers were then observed for only 24 hours. The EPA reviewers assessments of the studies indicate that the toxicity of MBI-206 to all insect species tested is inconclusive.

7 Ms. Nora Mealy 7. Additional toxicity information was submitted that partially addresses data gaps identified by BOH. There is no indication given in the Marrone document regarding the validity or acceptability of the studies to satisfy either U.S. or European data requirements. Many of the studies submitted for consideration in the first Venerate XC submission were classified as being invalid or unacceptable by EPA. Four of the five invertebrate studies are new to BOH, the fifth, a Daphnia acute test, was previously submitted: Two Honey bee studies with new EPA DER numbers, conducted using the enduse product, show no toxicity at a limit dose of 1000 µg/bee. A predatory mite, Typhlodromus pyri, study yielded 57% mortality at a 35lb ai/acre application rate. No EPA MRID number given. An aphid parasitoid wasp Aphidius rhopalosiphi test yielded an LR50> 34 lbs. ai/a, and an ER50 = 12 lbs. ai/a. No EPA MRID number given. The mite and wasp study were conducted according to standard test methods the descriptions of which are attributed to several authors. Both studies were conducted to support registration in the EU, though no OECD guideline numbers were reported for them. Results for 2 algae studies are reported. For the freshwater green algae, P. subcapitata, the 72 hr EC50>1000mg/L, NOEC = 160 mg/l. For the bluegreen algae Anabaena sp. the EC50>1000 mg/l for growth, EC50= 609 mg/l for yield, and NOEC=160 mg/l. Non-Target Plants Table 1 lists herbicidal activity for all 6 of the identified metabolites in MBI-206. The 2 plant toxicity studies for which DERs were submitted are classified as Inconclusive/Incomplete and Invalid/Incomplete respectively. The first study is identified as a Vegetative Vigor study EPA MRID No A single application of MBI-206 was made at either the maximum label rate of 2 gallons/acre or 2.5X the maximum rate using water as the carrier. The study was not conducted according to EPA Guideline requirements and did not produce an IC25 value. An IC25 is the treatment rate at which a species vegetative vigor is inhibited by 25%. At both the maximum label rate of 2 gallons/acre and the 2.5X rate to soybean, radish, cabbage, cucumber, and lettuce, the symptoms of phytotoxicity had a statistically significant increase at 7 days after treatment (DAT). The same result was observed at 15DAT, except for lettuce, which was affected by a general decline in plant health. The second study is identified as Nontarget Plant Testing, Tier I EPA MRID The reviewer states in the classification section of the DER that This study is not quantitative and is of insufficient duration and sample size to assess potential risks to nontarget plants outside of intended agricultural environments. A single application of MBI-206 was made to test plants at either 1 gallon ai/acre (1X) or 3.3 gallons ai/acre (3.3X). Species tested include monocots (wheat, corn, sorghum, onion, barley) and dicots (soybean, tomato, green bean, broccoli, cucumber, and peas). Phytotoxicity ratings for monocots ranged from none to mild during the 7-day study at the 1X rate, and from mild to moderate at 3.3X. Phytotoxicity ratings

8 Ms. Nora Mealy 8. for dicots (except soybean) ranged from none to moderate at 1X, and from mild to severe at the 3.3X rate. The phytotoxic symptom for soybean was outgrow by the end of the 7-day study. Exposure Environmental fate information was not originally submitted with the MBI-206 data package. The Environmental Risk Assessment dated December 13, 2013 conducted by the EPA Biopesticides and Pollution Prevention Division (BPPD), states that the field stability of the heat-killed active ingredient is not known. The later BPPD Biopesticides Registration Action Document states that further testing is not required. In response to the BOH request for a description of the environmental fate of the Venerate XC active ingredient, Marrone submitted results from an Assessment of Ready Biodegradability-Sealed Vessel Carbon Dioxide Evolution test. OECD guideline 310, OPPTS guideline In vessels containing Venerate XC the CO 2 produced after approximately Day 7 represented 84.5% of the theoretical maximum, which increased to 91.9% by Day 28 of the test. Based on this, Venerate XC was considered to be readily biodegradable. No other information was provided. The materials submitted to date do not provide the information necessary to assess risks associated with Venerate XC labeled use with an acceptable degree of confidence. There is no information on the amount of the identified 6 bioactive compounds contained in Venerate XC, and too little information on what happens to them post application. The biodegradation test tells us that approximately 92% of the organic carbon in the test vessels is metabolized to CO 2 within 28 days, nothing else. There is no way to know if the 8% that remains is made up of the bioactive compounds or not. In addition, there are no physical or chemical data on those 6 compounds, therefore, it is not known how mobile, volatile, or soluble they are. Concerns remain regarding aerial application and use on crops adjacent to known listed species locations. Screening Exposure Modeling Conservative non-target organism exposure modeling was conducted for Venerate XC label uses relevant to NYS. The high allowable Venerate XC application rates and unknown toxicity test result in a large measure of uncertainty in estimates of risk to non-target organisms. Summary and Risk Assessment The Venerate XC data package submitted to BOH did not include environmental fate, and aquatic macrophyte and/or algae data. Venerate XC when used as labeled does not appear to pose an undue risk to vertebrate nontarget organisms. It is unknown if Venerate XC poses an undue risk to nontarget insects, aquatic macrophytes, or algae. The Venerate XC label allows repeat applications at 3-10 day intervals with no upper limits stated. Single applications equaling roughly 2 pounds ai per acre to 15.8 pounds ai per acre are allowed by the label. Assuming a 180 day growing season, if applied as labeled, at 3 day intervals, it equals pounds of ai per acre per season and pounds of ai per

9 Ms. Nora Mealy 9. acre per season if applied at 10 day intervals. Information describing the anticipated amount used through a normal growing season in NYS would be helpful. Marrone Bio Innovations supplied a description of typically expected NY field use rates. While the label technically allows application of 8 quarts Venerate per acre at 3 day intervals with no upper limit stated, equaling roughly 946 pounds of active ingredient per acre per year, lbs. ai/a/yr, that rate would cost a user around $5,000 per acre which is not economically feasible. A typical preventative usage on labeled NY crops, as per Marrone, would consist of applications of 2-4 qts./a with 2 to 4 treatments per growing season equaling 8-32 lbs. ai/a/yr. Curative treatments during severe infestations may require the 8 qt./a rate at intervals dictated by the pest responses in each particular case. Application of the higher allowed rates should be the exception rather than the norm. Given the unknown fate and unknown toxicity range, Venerate XC may put at undue risk the 8 Endangered, 1 Threatened, and 9 Special Concern lepidopteran species which are known to inhabit NY State. BOH staff objects to the registration of this product as labeled due to risks to non-target resources. Concerns may be mitigated by prohibiting the following: aerial application, ground (foliar) application within 100 feet of surface water; and use on crops that border known listed (Endangered, Threatened, and Special Concern) plant or insect species locations.