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Bacillus subtilis Strain QST 713 (006479) Biopesticide Registration Action Document

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Issued: 6/00

On This Page

  1. Executive Summary
  2. Overview
    1. Product Overview
    2. Use Profile
    3. Regulatory History
  3. Science Assessment
    1. Physical and Chemical Properties Assessment
    2. Human Risk Assessment
    3. Environmental Assessment
  4. Non Target Risk Assessment
    1. Avian
    2. Non-Target Insects
    3. Freshwater Aquatic Invertebrate
    4. Freshwater Fish
    5. Non Target Plants
    6. Other Non-Target Organisms
  5. Efficay
  6. Public Interest Findings
  7. Risk Management and Registration Decision
    1. Determination of Eligibility
    2. Regulatory Position
    3. Labeling Rationale
  8. Actions Required by Registratns
    1. Precautionary Labeling
    2. Environmental Hazards Labeling
    3. Labeling
    4. Data Necessary to Support a Conditional Registration
  9. Bibliography

  1. Executive Summary

    2. Bacillus subtilis strain QST 713 as an active ingredient is a biological control agent for use on several minor crops to treat a variety of plant diseases and fungal pathogens including gray mold, powdery mildew, early and late blight, bacterial spot, and walnut blight. Bacillus subtilis is a ubiquitous bacteria commonly found in various ecological niches including soil, water and air which does not have a history of pathogenicity from contact in the environment. In addition, there are other strains of B. subtilis which are registered as microbial pesticides.

    Sufficient data are available to determine that Bacillus subtilis strain QST 713 has low toxicity to mammals and is not expected to be pathogenic in humans. Standard personal protective equipment are required to mitigate any risk to pesticide handlers and applicators. No significant risk is expected from the terrestrial ground application of the end-use product to birds, fish, ladybird beetles, green lacewings, honeybees, parasitic wasps, and aquatic invertebrates. Risks to honeybees have been mitigated by requiring that the end-use product not be applied when bees are actively visiting the treatment area and not allowing certain bee-sensitive crops (apples and pears) on the label.

    The data submitted to EPA on B. subtilis strain QST 713 are adequate to support a 2 year time-limited conditional registration under FIFRA section 3(c)(7)(C). A whole hive honeybee study is being required as a condition of registration. In addition as a term and condition of registration, the Agency is requiring a specific manufacturing process including an analysis of each batch for particular microbial contaminants. Additional product characterization studies, including storage stability studies will be required if the registrant applies to amend their registration to eliminate the required manufacturing process and batch analysis. In addition, the Agency is requiring confirmatory data on some ecological effects studies to further evaluate the pathogenicity potential of this strain of B. subtilus to non-target organisms.

    The acute oral toxicity, acute dermal toxicity, acute pulmonary, acute intravenous, primary eye irritation, primary dermal irritation, and delayed contact hypersensitivity test are acceptable. The acute pulmonary study showed no mortality and no adverse effects when performed using the technical product. There was also no mortality from the acute inhalation study using the end-use product although some clinical signs and weight loss were noted. However, the acute inhalation study did not measure the actual concentration of the product in the test. Considering that the particle size of the wettable powder poses a low risk of inhalation exposure and the nature of the inerts in the product, the Agency is using the acute inhalation study as confirmatory of the acute pulmonary study and waiving the requirement for a repeated acute inhalation study. In addition, any risk is mitigated by standard personal protective equipment and the reentry interval required for the end-use product.

    Extremely high levels of the bacteria were used in the ecological effects testing. The levels far exceeded what will typically be used in the field. These high test concentrations resulted in mortality which complicated interpretation of the studies. Toxicity was not considered significant except for the honeybee study where mortality was seen at all test concentrations. There were numerous reports from researchers and bee keepers indicating that no adverse effects were seen during experimentation. As a condition of registration, EPA is requiring that the registrant conduct a whole hive study following an EPA approved protocol. Until this data can be generated, reviewed by EPA, and a determination is made that honeybees are not at risk from the use of QST 713, use sites where bees would be exposed are prohibited and a honeybee warning statement is required. EPA test guidelines for non-target organisms recommends that if toxicity is found, a pathogenicity test also be conducted. Given the very high doses at which toxicity occurred in the honeybee study, it is unclear whether the effect is from toxicity alone or combined with pathogenicity. For the non-target tests in freshwater fish, aquatic invertebrates, honeybees, and hymenoptera where mortality was reported at high dose levels, EPA is requiring a confirmatory pathogenicity test be conducted and EPA is recommending that the tests be conducted at more reasonable concentrations.

    In addition, the submitted manufacturing process did not have sufficient quality control required for all fermentation batches. Therefore, as a term and condition of this registration, EPA has established criteria each batch of product must meet in order to be marketed. Results of these batch tests will be submitted to EPA upon request. A listing of the required data are given on pages 27 to 28.

    The submitted data in support of this registration under section 3(c)(7)(C) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) have been reviewed and determined to be adequate for a time-limited two (2) year registration. This registration will not cause unreasonable adverse effects to man or the environment.

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  2. Overview

    1. Product Overview

      • Microbial Pesticide Name: Bacillus subtilis strain QST 713


      • Trade Name(s): QST 713, SerenadeTM

      • OPP Chemical Code: 006479


      • Basic Manufacturer: AgraQuest, Inc., 1530 Drew Ave., Davis, CA 95616

    2. Use Profile

      1. Type of Pesticide: Biological control agent, Microbial Fungicide


      2. Mechanism of action: The bacterium, Bacillus subtilis, is prevalent in soils and has been found in a variety of habitats worldwide. The QST 713 strain of B. subtilis is known to be antagonistic toward many fungal plant pathogens. This antagonism may be achieved in several ways including nutrient competition, site exclusion, colonization and attachment of the bacteria to the fungal pathogen. In addition, AgraQuest reports that the QST 713 strain of B. subtilis has been shown to induce plants' natural systemic resistance or systemic acquired resistance (SAR) against bacterial pathogens. These bacteria can stop plant pathogen spores from germinating, disrupt germ tube growth and inhibit attachment of the plant pathogen to the leaf.


      3. Use Sites: Terrestrial Food: cherry, cucurbits, grapes, hops, leafy vegetables (except Brassica), peanuts, peppers, potatoes, tomatoes, walnut


      4. Target Pests for Active Ingredient: Powdery mildew (Podosphaera leucotricha, Uncinula necator, Sphaerotheca macularis, Oidiopis taurica, Leveillula taurica); Gray mold (Botrytis cinerea); Downy mildew (Plasmopara viticola, Bremia lactucae, Peronospora spp.); Early Blight (Alternaria solani); Late Blight (Phytophera infestans); Bacterial spot (Xanthomanas spp); Walnut blight (Xanthomanas campestris)


      5. Formulation Types Registered:


        • Type: Technical and End-Use Product
        • Form: 10% Wettable Powder; 14.6% Technical Powder


      6. Method and Rates of Application:


        • Types of Treatment: Ground spray
        • Equipment: not specified
        • Rates of Application: 3 to 10 lbs per an acre (rate varies depending on crop), number of applications unspecified

    3. Regulatory History

      4. graQuest Inc. submitted an application August 24, 1998 for registration of Serenade Biofungicide Wettable Powder and QST 713 Technical along with a pesticide petition which proposed establishing an exemption from the requirement of a tolerance for residues of the microbial pesticide, strain QST 713 of Bacillus subtilis, on growing crops.

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  3. Science Assessment

    1. Physical and Chemical Properties Assessment

      2. Product Identity:

      The Agency has classified Bacillus subtilis strain QST 713 as a microbial pesticide. Serenade Biofungicide Wettable Powder and QST 713 Technical contain living Bacillus subtilis strain QST 713 as the active ingredient. Bacillus subtilis is a rod-shaped, gram positive, aerobic, motile (peritrichous flagella) bacterium which is ubiquitous in nature. Bacillus subtilis is commonly found in various ecological niches including soil, water and air. The bacterium commonly produces proteases and other enzymes and because of this, strains of the bacterium are commonly used for industrial production of enzymes and other chemicals. The bacterium also can produce an endospore which allows the organism to endure extreme environmental conditions (e.g. heat, drought).

      The genus Bacillus is a large, diverse genus of bacteria that includes species such as thuringiensis, licheniformis, pumilis, cereus and anthracis. Two of these species, B. cereus and B. anthracis, are known to be pathogenic to humans and animals. Because of this, the ability to differentiate species is extremely important. Biochemical tests and other tools exist which allow for the proper identification of the organism in question, B. subtilis. Product chemistry data which support the registration of Bacillus subtilis strain QST 713 are summarized in Table 1. The manufacturing process, formation of unintentional ingredients, and analysis of samples are acceptable because of the performance standard.

      The Agency is waiving the requirement for storage stability studies at this time, but the Agency will require these studies before it will approve a change in the required manufacturing process including the requirement to test each batch for microbial contamination. Storage stability studies are conducted on the end-use product manufactured for commercial use to insure that the product does not degrade and cause an unreasonable adverse effect as well as to determine that the microorganisms remain viable for the shelf life of the product. For microbial pesticide products where small fermentation systems used during the experimental stages are not the final, larger fermentation systems used for producing the commercial product, storage stability studies typically must be performed on the end-use product as manufactured for commercial use in the field. The Agency has determined that if the QST 713 products are produced using the manufacturing process and quality criteria required, there is a reasonable certainty that no adverse effects will occur during the time of the conditional registration.

      Table 1. Physical and Chemical Properties for Bacillus subtilis QST 713 Technical
      OPPTS GUIDELINE Number STUDY RESULT MRID#
      885.1100 Product Identity and Disclosure of Ingredients ACCEPTABLE 44651702, 44651704, 44651703, 45084501
      885.1200 Manufacturing Process ACCEPTABLE when batches meet EPA set criteria.

      Additional data needed to eliminate term on every batch testing to meet criteria.

      		 44651904
      885.1300 Formation of Unintentional Ingredients ACCEPTABLE when the manufacturing process required by EPA is followed and the required QA/QC is performed.

       

      44651904, 45084501
      885.1400 Analysis of Samples ACCEPTABLE when the manufacturing process required by EPA is followed, the required QA/QC is performed, and each batch is tested for microbial contamination. 44651902
      885.1500 Certification of Limits ACCEPTABLE 45084501
      830.6302, 830.6303, 830.6304, 830.7000, 885.7300 Product Chemistry ACCEPTABLE except for Storage Stability. Storage stability data are SUPPLEMENTAL and may be upgraded with submission of additional data. 44651901

      44651903
      Additional manufacturing process data are required as a condition of registration. Details concerning requirements are discussed in a Confidential Business Information Appendix.

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    2. Human Risk Assessment



      1. Human Toxicity Assessment

        2. The acute oral toxicity, acute dermal toxicity, acute pulmonary, acute intravenous, primary eye irritation, primary dermal irritation, and delayed contact hypersensitivity test are acceptable. The acute pulmonary study showed no mortality and no adverse effects when performed using the technical product. There was also no mortality from the acute inhalation study using the end-use product although some clinical signs and weight loss were noted. However, the acute inhalation study did not measure the actual concentration of the product in the test. Considering that the particle size of the wettable powder poses a low risk of inhalation exposure and the nature of the inerts in the product, the Agency is using the acute inhalation study as confirmatory of the acute pulmonary study and waiving the requirement for a repeated acute inhalation study. In addition, any risk is mitigated by standard personal protective equipment and the reentry interval required for the end-use product.

        Table 2. Toxicity Data Requirements
        OPPTS GUIDELINE Number STUDY RESULT MRID#
        885.3050 Acute Oral Toxicity/ Pathogenicity Acceptable, Toxicity Category IV 44651906
        885.3100 Acute Dermal Toxicity/ Pathogenicity LD50 of QST 713 Technical in rats is >2g /kg body weight.
        Acceptable Toxicity Category III        		 44651907
        885.3150 Acute Pulmonary Toxicity/ Pathogenicity Acceptable. No mortality and no adverse effects. The test microbe was detectable (both pre- and post- heat treatments) in the lung through Day 35, but at significantly reduced levels compared to day 0. 44651909
        870.1300 Acute Inhalation

        (End-Use Product WP)        		 Study considered confirmatory for the acute pulmonary study. Some clinical signs and weight loss were noted, but no mortality resulted from dosing. The actual concentration was not determined.

        Normally, particles the size of those measured for QST 713 wettable powder pose a low risk of inhalation exposure. Study results could be enhanced with analytical data indicating the actual concentration used in dosing.

        Potential risk is mitigated by protective clothing requirements of a dust/mist filtering respirator and the reentry interval.        		 44652705
        885.3200 Acute Intravenous Toxicity/Pathogenicity Acceptable No mortality and no adverse clinical signs in rats dosed with QST 713 technical powder. The test microbe cleared from most organs by day 35; however, low levels detected in spleen and liver after 35 days. 44651908
        870.2400 Primary Eye Irritation Acceptable, Toxicity Category III 44664602
        870.2500 Primary Dermal Irritation Acceptable, Toxicity Category IV 44664601
        870.2600 Delayed Contact Hypersensitivity in Guinea Pigs (QST 713 Wettable Powder) Acceptable - QST 713 WP product did elicit a very mild delayed hypersensitivity response. Potential dermal sensitizer 44664705

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      2. Toxicological Profile

        3. Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the available scientific data and other relevant information in support of this action and considered its validity, completeness, and reliability and the relationship of this information to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children.

        A battery of tests determined that QST 713 Technical product is not pathogenic and has no significant toxicity. The acute oral toxicity/pathogenicity, acute pulmonary toxicity/pathogenicity, and acute intravenous toxicity/ pathogenicity studies demonstrated no significant toxicity and a lack of pathogenicity. The dermal toxicity and eye irritation studies resulted in a Toxicity Category III classification. The acute dermal irritation study resulted in a Toxicity Category IV classification. Bacillus subtilis is a ubiquitous organism in the environment and there have been no reports of the organism affecting the immune system. The submitted toxicity/pathogenicity studies in rodents with Bacillus subtilis strain QST 713 indicated that following several routes of exposure, the immune system is still intact and able to process and clear the active ingredient. As would be expected for any microbial pesticide, QST 713 did elicit a very mild delayed hypersensitivity response and is considered a potential dermal sensitizer. Further, although it is not known whether strain QST 713 does, the species is known to produce the enzyme subtilisin which has been reported to produce allergenic or hypersensitivity reactions to individuals repeatedly exposed to the enzyme in industrial settings. The use of personal protective equipment required for applicators and other handlers mitigates the hypersensitivity risk by minimizing exposure. No hypersensitivity risk is expected for dietary exposure due to the low likelihood that any significant residues will occur on treated food.

      3. Aggregate Exposures

        4. In examining aggregate exposure, FFDCA section 408 directs EPA to consider available information concerning exposures from the pesticide residue in food and all other non-occupational exposures, including drinking water from ground water or surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses).

        1. Dietary Exposure

          2. Dietary exposure to the microbial pesticide is likely to occur, however the lack of acute oral toxicity/pathogenicity and the ubiquitous nature of the microbial, support the establishment of an exemption from the requirement of a tolerance for Bacillus subtilis strain QST 713.

          1. Food. Dietary exposure to the microbial is expected to be minimal. The risk posed to adults, infants and children is minimal because of the low acute oral toxicity/pathogenicity potential of the microbial pesticide. In addition, standard practices of washing, peeling, cooking or processing fruits and vegetables reduces residues of Bacillus subtilis strain QST 713 and further minimizes dietary exposure.


          2. Drinking water exposure. Oral exposure, at very low levels, may occur from ingestion of drinking water. Drinking water is not being screened for Bacillus subtilis strain QST 713 as a potential indicator of microbial contamination. Both percolation through soil and municipal treatment of drinking water would reduce the possibility of exposure to the bacterial active ingredient through drinking water. If oral exposure should occur through drinking water, the Agency concludes that such exposure would present insignificant risk due to the lack of acute oral toxicity/pathogenicity and the ubiquitous nature of the microbe.


        2. Other Non-Occupational Exposure

          3. The use sites proposed are for agricultural sites. Dermal and inhalation exposure is expected to be limited to those who apply or handle the pesticide in orchards and farms. Bacillus subtilis presence is ubiquitous in the environment and the use of this product is not expected to increase dermal or inhalation exposure in non-occupational settings.

      4. Cumulative Effects

        5. No mechanism of toxicity in mammals has been identified for Bacillus subtilis strain QST 713. Therefore no cumulative effect with other related organisms is anticipated. Because the data available demonstrate a low toxicity/pathogenicity potential of the active ingredient, the likelihood of adverse dietary effects is expected to be minimal.

      5. Determination of Safety for U.S. Population, Infants and Children

        6. Based on the acute toxicity information discussed above, EPA concludes that there is a reasonable certainty that no harm will result from aggregate exposure to the United States population, including infants and children, to residues of Bacillus subtilis strain QST 713 . This includes all anticipated dietary exposures and all other exposures for which there is reliable information. The Agency has arrived at this conclusion because, the data available on Bacillus subtilis strain QST 713 demonstrate a low toxicity/pathogenicity potential. Bacillus subtilis is not a human pathogen and has not been implicated in human disease, but has been isolated as a rare contaminant from human infections. Risk of increased exposure is likely only to exist for pesticide applicators and manufacturers of the product. The Agency has imposed appropriate risk mitigation measures to protect the workers via the use of protective clothing.

      6. Other Considerations


        1. Endocrine Disruptors

          2. The Agency has no information to suggest that Bacillus subtilis strain QST 713 has an effect on the endocrine system. No specific tests have been conducted with Bacillus subtilis strain QST 713 to determine such effects. However, the submitted toxicity/pathogenicity studies in rodents indicated that following several routes of exposure, the immune system is still intact and able to process and clear the active ingredient. Bacillus subtilis strain QST 713 is a ubiquitous organism in the environment and there have been no reports of the organism affecting endocrine systems. Therefore, it is unlikely that this organism would have estrogenic or endocrine effects because it is practically non-toxic to mammals.

        2. Analytical Method(s)

          3. The Agency proposes to establish an exemption from the requirement of a tolerance without any numerical limitation; therefore, the Agency has concluded that an analytical method is not required for enforcement purposes for Bacillus subtilis strain QST 713.

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    3. Environmental Assessment



      1. Environmental Fate

        2. B. subtilis is common in soil and plant litter without documented toxicity or pathogenicity in the environment. When B. subtilis was used as a tracer in ground water studies it was noted that it moves faster than rhodomine WT dye in an alluvial gravel aquifer. B. subtilis endospores are reported as having longevity in ground water (Pang, L; Close, M. and ; Noonan, M; 1998).

      2. Ecological Toxicity

        3. Following ecological effects data requirements listed in 40 CFR Part 158 for microbial pesticides, studies were conducted on birds, fish, non-target insects, aquatic invertebrates, and non-target plants using B. subtilis strain QST 713. As described below, QST 713 was determined to be practically non-toxic to bobwhite quail and the risk quotients for fish were far below the levels of concern. Exposure to aquatic sites and organisms (fish and aquatic invertebrates) are minimal to non-existent. There are no aquatic use sites and application methods are restricted to ground sprays. No phytotoxicity was reported at the specified label rates. Bacillus subtilis is a very well studied microorganism and no evidence of fish or aquatic invertebrate toxicity or pathogenicity was found in published literature. However, additional data on freshwater fish, aquatic invertebrates, parasitic hymenoptera, and Paleomonetes vulgaris to evaluate pathogenicity potential of B. subtilis strain QST 713 are required.

        Extremely high levels of the bacteria were used in the non-target insect testing which exceed the amount which would be used in the field. These high test concentrations resulted in mortality which complicated interpretation of the studies. In only one case (honeybees), did all test concentrations show treatment related mortality. The honeybee study is very difficult to conduct without mortality because bees are removed from their hive and queen to be exposed to the pesticide. Mortality in controls as well as from treatment are common in honeybee tests and were seen in this case also. In addition, this test was conducted for a shorter duration than recommended in EPA guidelines. Although toxicity was observed in the laboratory studies, numerous researchers and beekeepers reported to EPA that no bee mortality was observed in the field during the experimental trials. The potential risk to honeybees will be mitigated by prohibiting use of QST 713 on certain bee-sensitive crops such as apples and pears and a bee warning statement on the label until additional data such as a whole hive study is conducted and reviewed to determine bees are not at risk from use of this pesticide.

        Toxicity was observed at very high concentrations for parasitic hymenoptera. EPA guidelines, which provide registrants with guidance for conducting studies, recommend that if mortality is observed, that pathogenicity tests be conducted. Because these tests were not conducted, EPA is requiring confirmatory testing on parasitic hymenoptera.

        Table 3. Summary of Submitted Data
        GRN MRID # Study Status, Classification & Comments
        885.4050 44651910 Avian Oral (Quail) The avian oral LD50 is greater than 5000 mg/kg body weight. QST 713 Technical containing B. subtilis strain QST 713 is considered practically non-toxic to bobwhite quail due to the high dose used and the effects observed. The 1 bird mortality and the 7 other birds exhibiting signs of clinical toxicity were considered due to toxicity at the high dose administered

        CLASSIFICATION: Acceptable.
        154-17   Avian Injection test Not required since B. subtilis is not a bird pathogen and signs of pathogenicity were not demonstrated in the avian oral study.
        885.4200 44884801 Freshwater Fish Toxicity/

        Pathogenicity        		 Given the plate count patterns observed, it is probable that the actual concentrations trout were exposed to were not more than 12 orders of magnitude lower than the nominal concentrations. An approximate LC50 using the binomial method was 2.62 x 108 CFU/L (13.1 mg/L) with 95% confidence limits of 1.12 x 108 CFU/L (5.6 mg/L) and 4.2 x 108 CFU/L (21 mg/L). A precise LC50 could not be determined because there were less than 2 concentrations at which the percent dead were between 0 and 100. The NOEC was 1.12 x 108 CFU/L (5.6 mg/L). Since only necropsy of randomly chosen surviving trout occurred at study termination, we can not at this time conclude that only toxicity was involved in the mortality observed since pathogenicity was not ruled out by appropriate analysis.

        CLASSIFICATION: Acceptable with required confirmatory data. Data considered confirmatory because Bacillus subtilis is very well studied and no evidence of fish toxicity or pathogenicity was found in published literature. In addition, exposure to aquatic organisms are minimal to non-existent ( no aquatic use sites and application methods are restricted to ground sprays).
        885.4240 446519B12 48-Hour Freshwater Aquatic Invertebrate Toxicity/

        Pathogenicity        		 An estimated environmental concentration (EEC) was calculated to be 2.5 x 104 CFU/L. The acute aquatic risk quotient was calculated to be 0.00083, well below the level of concern.

        The study is considered Acceptable, although a confirmatory study is required to determine the pathogenicity using attenuated and filter sterilized controls. Data considered confirmatory because Bacillus subtilis is very well studied and no evidence of aquatic invertebrate toxicity or pathogenicity was found in published literature. In addition, exposure to aquatic organisms are minimal to non-existent ( no aquatic use sites and application methods are restricted to ground sprays)
        885.4240 446519B13 21-Day Freshwater Aquatic Invertebrate Toxicity/

        Pathogenicity        		 The LC50 was determined to be greater than 3 x 107 CFU/L (1.5 mg/L). The cause of death and whether pathogenicity was involved was not determined. An estimated environmental concentration (EEC) was calculated to be 2.5 x 104 CFU/L. The chronic aquatic risk was calculated to be 0.0033, well below the level of concern.

        The study is considered Acceptable, although a confirmatory study is required to determine the pathogenicity using attenuated and filter sterilized controls. Data considered confirmatory because Bacillus subtilis is very well studied and no evidence of aquatic invertebrate toxicity or pathogenicity was found in published literature. In addition, exposure to aquatic organisms are minimal to non-existent ( no aquatic use sites and application methods are restricted to ground sprays)
        885.4300 None Non-Target Plant Study This data requirement is waived because a review of scientific literature does not indicate that Bacillus subtilis is a common pathogen or phytotoxic agent.

        AgraQuest has reported (5/12/99 and 4/28/2000 facsimile of field trial summaries) no phytotoxicity when was applied as a foliar spray to the following crops in various countries: almonds, crookneck and acorn squash, watermelon, mushroom, nectarine, peanut, pistachio, potato, strawberry, and tomato.

        A minimal amount of foliar marginal necrosis and berry scarring was reported at a 17 lbs/acre rate in grapes. However, no phytotoxicity in grapes was observed at the current label rate of 8 lbs.

        The registrant is to inform the Agency of any incidents of damage to crops or non-target plants as a result of registered uses of Serenade for further hazard evaluation.
        885.4340 44651916 Non-Target Insect Study-Green Lacewing The study is acceptable and fulfills the guideline requirement. The mortalities observed were not treatment related and the LC50 was greater than 60,000 ppm. However, due to decreased pupation, the no observed effect concentration (NOEC) was 600 ppm (1.2 x 107 CFU/g).

        CLASSIFICATION: Acceptable.
        885.4340 44651915 Non-Target Insect Study -Ladybird Beetle The study is acceptable and fulfills the guideline requirement. The mortalities observed were not treatment related and the LC50 was greater than 60,000 ppm. The no observed effect concentration (NOEC) was 60,000 ppm (1.2 x 109 CFU/mL).

        CLASSIFICATION: cceptable.
        885.4380 44651917 Honeybee Dietary Toxicity/

        Pathogenicity        		 A five day LC50 of 5663 ppm was calculated using the moving average method after data adjustment via Abbott's formula to compensate for control mortality. All test concentrations showed treatment related mortality, including the concentration reported to be the estimated environmental concentration. The study is supplemental due to the short test duration and the lack of a determination as to whether mortality was due to toxicity only or whether pathogenicity contributed. A 30-day whole hive study is necessary to satisfy this guideline requirement.

        CLASSIFICATION: Supplemental. Although the data is supplemental, the requirement is satisfied for a two (2) year conditional registration that requires the end-use product label to state "Do not apply this product to allow it to drift to blooming crops or weeds while bees are actively visiting the treatment area."
        885.4340 44651914 Non-Target Insect Study -Parasitic Hymenoptera QST Technical was shown to cause mortality to parasitic Hymenoptera. The dietary LC50 for 15 days is calculated as being approximately 28,000 ppm by the moving average method with 95 percent confidence intervals of approximately 18,000 ppm and 51,000 ppm. This is more than 100 times the EEC so toxicity is not considered significant. However, potential pathogenicity was not investigated.

        CLASSIFICATION:Acceptable with confirmatory data required.

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  4. Non Target Risk Assessment

    1. Avian

      2. The avian oral LD50 is greater than 5000 mg/kg body weight. QST 713 Technical containing B. subtilis strain QST 713 is considered practically non-toxic to bobwhite quail. The data requirement is satisfied for Bobwhite quail. The mallard study (for guideline 885.4050) is waived based on the lack of avian pathogenicity in the literature and the limited toxicity observed in the quail study.

    2. Non-Target Insects



      1. Honey Bee

        2. A five day LC50 of 5663 ppm was calculated using the moving average method after data adjustment via Abbott's formula to compensate for control mortality. Estimated environmental concentrations (EECs) were estimated via the Kenega nomogram which provides expected residue levels on terrestrial food/feed items. The most appropriate substrates for a honey bee assessment are "leaves and leafy crops" and "forage, alfalfa, clover." Based on a single application at the 10 lb product /acre, the EECs for the technical grade active ingredient are 250 ppm and 115 ppm. Thus, the LC50 of 5663 ppm is approximately twenty-two (22) times the EEC based on foliar residue. Bees directly sprayed with QST 713 would be exposed to approximately 8000 ppm. The risk mitigating label statement, "Do not apply this product or allow it to drift to blooming crops or weeds while bees are actively visiting the treatment area," effectively reduces the exposure to bees to a level below the lowest observable effect concentration (LOEC) of 600 ppm in the honey bee study.

        The EPA guideline study is difficult to conduct without mortality to control as well as treated bees in part because the bees are separated from the queen and the rest of the hive. This study is rated supplemental due to the short test duration and the lack of a determination as to whether mortality was due to toxicity only or whether pathogenicity contributed. Although the study is supplemental, the risk to honeybees has been mitigated by a label statement for the end-use product label to read "Do not apply this product to allow it to drift to blooming crops or weeds while bees are actively visiting the treatment area" and prohibition of apples and pears as use sites. A whole hive study is being conditionally required. The registrant must submit a protocol for EPA review before initiating the study.

        Nineteen individuals who participated in field trials of the end-use product of this active ingredient, SerenadeTM WP Biofungicide submitted letters attesting that they observed no negative effect to bees. The field testing performed was designed to research efficacy and phytotoxicity. In many but not all cases a hive was located at the sites at time of treatment. EPA contacted the individual researchers to obtain clarification and locate beekeepers whose bees were exposed to the microbial product. None of these were formal studies designed to investigate the effects this microbial product may have on honeybees. However, their observations and of the beekeepers who had hives exposed to Bacillus subtilis strain QST 713 provide some information about its lack of reported effects to bees in actual field conditions. A summary of the information collected is below.

        Beekeeper Interview Summary

        Three beekeepers whose bees were exposed at field trials of Serenade report that no problems were noted. They all indicated that written records were not usually taken unless a problem was noted. One of them reported giving special examination to a hive because of a hive kill one mile away where insecticides were applied. In addition, hives are subject to inspection by county or state bee agents. Due to the migratory nature of this profession, there were difficulties locating other beekeepers.

        Summary of Letters and Interviedws of Researchers

        Nineteen agricultural researchers submitted letters. Several indicated some applications were made at bloom. They reported:
        1. No increase of honeybee mortality was observed in the field or by the hives;
        2. No difference in foraging or activity before and after application;
        3. Honeybees were not avoiding material;
        4. No negative effects on pollination observed at apple, pear, cherry, cucurbit, strawberry, grape. snap beans, bell pepper, potato, and watermelon;
        5. Cucurbits which are entirely dependent on bees for pollination produced normal yields; And
        6. They received no complaints from beekeepers or orchardist.
      2. Parasitic hymenoptera

        3. QST Technical was shown to cause mortality to parasitic Hymenoptera (Nasonia vitripennis). The dietary LC50 for 15 days was calculated as being approximately 28,000 ppm by the moving average method with 95 percent confidence intervals of approximately 18,000 ppm and 51,000 ppm. The LOEC was 600 ppm. Estimated environmental concentrations (EECs) were estimated via the Kenega nomogram which provides expected residue levels on terrestrial food/feed items. Based on a single application at the 10 lb product /acre, the EECs for the technical grade active ingredient are 250 ppm and 115 ppm. Thus, the LC50 of 28,000 ppm is approximately one hundred and twelve (112) times the EEC based on foliar residue. Parasitic wasps directly sprayed with QST 713 would be exposed to approximately 8000 ppm. Given the high LC50 of 28,000 ppm, the risk to parasitic wasps is not significant. The study is graded acceptable with required confirmatory data to evaluate potential pathogenicity.

      3. Ladybird beetle

        4. The study is acceptable and fulfills the guideline requirement. The mortalities observed were not treatment related and the LC50 was greater than 60,000 ppm. The no observed effect concentration (NOEC) was 60,000 ppm (1.2 x 109 CFU/mL). Data requirement is satisfied. The risk to ladybird beetles from the use of the end-use product SerenadeTM is not considered significant.

      4. Green lacewing

        5. After QST Technical treatment, the mortalities observed were not treatment related and the LC50 was greater than 60,000 ppm. However, due to decreased pupation, the no observed effect concentration (NOEC) was 600 ppm (1.2 x 107CFU/g). The LOEC was 6000 ppm or 24 times the EEC of 250 ppm. The data requirement is satisfied. The risk to green lacewing from the use of the end-use product SerenadeTM is not considered significant.

    3. Freshwater Aquatic Invertebrate

      4. The 21-day LC50 was determined to be greater than 3 x 107 CFU/L (1.5 mg/L). The lowest observable effect concentration (LOEC), based on reproduction, mean length and mean dry weight was determined to be 1.5 x 107 CFU/L (0.75 mg/L). The NOEC was determined to be 7.5 x 106 CFU/L (0.38 mg/L). The cause of death and whether pathogenicity was involved was not determined.

      An estimated environmental concentration (EEC) was calculated using some of the same assumptions used in the GENEEC model. Namely, 1) runoff from a ten hectare field into a one hectare by two meter pond is sufficient to remove 10% of the pesticide from the ten hectare area after two days; and 2) direct spray drift into the pond at the time of application is 1% for ground application. The EEC was calculated to be 2.5 x 104 CFU/L.

      The acute aquatic risk quotient (EEC/LC50) was calculated to be (2.5 x 104/ 3 x 107) = 0.00083. Levels of concern for acute aquatic risk are 0.5 and 0.05.

      The chronic aquatic risk quotient (EEC/NOEL) was calculated to be (2.5 x 104/ 7.5 x 106 ) = 0.0033. The levels of concern for chronic aquatic risk is 1.

      Even though the risk quotients are far below the levels of concern and the risk to aquatic invertebrates from the terrestrial ground use of Serenade at 10 lbs/acre are considered minimal to nonexistent, we are requiring confirmatory data for potential pathogenicity. The pathogenicity data are considered confirmatory because Bacillus subtilis is very well studied and no evidence of aquatic invertebrate toxicity or pathogenicity was found in published literature.

    4. Freshwater Fish

      5. In the 30-day trout study, an approximate LC50 using the binomial method was 2.62 x 108 CFU/L (13.1 mg/L) with 95% confidence limits of 1.12 x 108 CFU/L (5.6 mg/L) and 4.2 x 108 CFU/L (21 mg/L). A precise LC50 could not be determined because there were less than 2 concentrations at which the percent dead were between 0 and 100. The NOEC was 1.12 x 108 CFU/L (5.6 mg/L). Since only necropsy of randomly chosen surviving trout occurred at study termination, we can not at this time conclude that only toxicity was involved in the mortality observed since pathogenicity was not ruled out by appropriate analysis.

      The EEC was calculated to be 2.5 x 104 CFU/L. Since the a precise LC50 could not be determined, the lower confidence limit of 1.12 x 108 CFU/L was used in risk calculation.

      The acute aquatic risk quotient (EEC/LC50) was calculated to be (2.5 x 104/1.12 x 108) = 0.000223. Levels of concern for acute aquatic risk are 0.5 and 0.05.

      The chronic aquatic risk quotient (EEC/NOEL) was calculated to be (2.5 x 104/1.12 x 108 ) = 0.000223. The levels of concern for chronic aquatic risk is 1.

      Even though the risk quotients are far below the levels of concern and the risk to fish from the terrestrial ground use of SerenadeTM at 10 lbs/acre are considered minimal to nonexistent, we are requiring confirmatory data to determine potential pathogenicity. The pathogenicity data are considered confirmatory because Bacillus subtilis is a very well studied and no evidence of fish toxicity or pathogenicity was found in published literature.

    5. Non-Target Plants

      6. This data requirement is waived because a review of scientific literature does not indicate that Bacillus subtilis is a common pathogen or phytotoxic agent. In addition, AgraQuest reported (5/12/99 facsimile) no phytotoxicity when Serenade was applied as a foliar spray to the following crops in various countries: almonds, crookneck and acorn squash, watermelon, mushroom, nectarine, peanut, pistachio, potato, strawberry, and tomato. A minimal amount of foliar marginal necrosis and berry scarring was reported at a 17 lbs/acre rate of Serenade on grapes. However, no phytotoxicity in grapes was observed at the current label rate of 8 lbs.

      The registrant is to inform the Agency of any incidents of damage to crops or non-target plants as a result of registered uses of Serenade for further hazard evaluation.

    6. Other Non-Target Organisms

      7. A strain of B. subtilis has been shown to be pathogenic to a terrestrial amphipod in New Zealand. [Duncan, K.W., (1981)]

      Due to the report of disease in a terrestrial amphipod crustacean, a 30-day toxicity /pathogenicity test in the shrimp Paleomonetes vulgaris is necessary per OPPTS Microbial Pesticide Testing Guideline OPPTS.885.4280 as a condition of these registrations to evaluate potential pathogenicity in crustacea.

      We note that 3 aquatic amphipods are currently listed as endangered. They are the Hay's Spring Amphipod (likely to occur in the District of Columbia), the Illinois Cave Amphipod (likely to occur in Monroe County, Illinois), and the Peck's Cave Amphipod (likely to occur in Comal County, Texas). These species are not expected to be impacted by the terrestrial use of B. subtilis strain QST-713 contained in pesticide products because this strain has not been identified as a pathogen to amphipods and any exposure would be extremely limited.

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  5. Efficay

    6. As no public health pests are listed as use sites, no efficacy data are required to be submitted or evaluated, although the registrant must continue to retain these studies.

  6. Public Interest Findings

    7. The Agency believes the use of Bacillus subtilis strain QST 713 under this conditional registration would be in the public interest. The criteria for Agency evaluation of public interest findings is outlined in 51 Fed.Reg. 7628-7634, Wednesday (March 5, 1986). As explained in part IV. A of that notice, the Agency presumes a pesticide is in the public interest if it is for minor use, is a unique replacement for pesticides of concern, or is for use against a public health pest.

    Bacillus subtilis strain QST 713 is intended for formulation into end-use products for control of a variety of plant pathogens including: Early Blight (Alternaria solani); Scab (Venturia spp.); and several types of mildew. Most of the uses are for minor use crops and therefore, the Agency presumes the pesticide is in the public interest. The Agency has determined that a naturally occurring microbial pesticide such as Bacillus subtilis strain QST 713 may provide an alternative which can reduce the hazards posed by conventional chemical pesticides. For these reasons the Agency concludes that, it is in the public interest to grant a conditional registration.

  7. Risk Management and Registration Decision

    1. Determination of Eligibility

      2. Data submitted are sufficient for the conditional registration under Section 3(c)(7)(C) of FIFRA of Bacillus subtilis strain QST 713 for the use patterns discussed in this document. The Agency will conditionally register this pesticide for a period of time reasonably sufficient for the generation and submission of additional studies that the Agency believes are required. Use of the pesticide during this period of conditional registration will not cause unreasonable adverse effects on the environment, and the use of this pesticide is deemed to be in the public interest.

      These conditional registrations will automatically expire in two (2) years. In order to be eligible for registration and to maintain registrations, the registrant must comply with all conditions specified under section VI.B.1.

    2. Regulatory Position



      1. Conditional Time-Limited Registration

        2. Section 3(c)(7)(C) of FIFRA provides for the conditional registration of new active ingredients if it is determined that 1) use of the pesticide during a defined period of time will not cause any unreasonable adverse effect on the environment; 2) use of the pesticide is in the public interest; and 3) that for the data that is lacking, a reasonable period of time sufficient for generation of the data has not elapsed since the Agency first imposed the data requirements.

        To satisfy criterion (1) above, it is believed that this new microbial pesticide will not cause any unreasonable adverse effects on human health or the environment. Sufficient data are available to determine that Bacillus subtilis strain QST 713 has low toxicity to mammals and is not expected to be pathogenic in humans when the product is used in accordance with label instructions. Standard personal protective equipment are required to mitigate any risk to pesticide handlers and applicators. No significant risk is expected from the terrestrial ground application of the end-use product Serenade to birds, fish, ladybird beetles, green lacewings, parasitic wasps and aquatic invertebrates. Risks to honeybees have been mitigated by requiring that the end-use product not be applied when bees are actively visiting the treatment area. To satisfy criterion (2) Bacillus subtilis strain QST 713 is for use on minor crops. Finally, the outstanding data was not identified in the new active ingredient screening process and a reasonable period for its generation has not yet passed.

        The data has been reviewed and BPPD has determined that a section 3(c)(7)(C) conditional registration that is limited in duration is appropriate in this situation. Data requirements for granting the subject time-limited registrations for terrestrial ground outdoor use under section 3(c)(7)(C) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) have been met. BPPD has determined that the use of this product will cause no unreasonable adverse effects to the environment if it is used pursuant to the following limitations.



        1. This registration will automatically expire on midnight July 1, 2002.


        2. Standard personal protective equipment are required to mitigate any risk to pesticide handlers and applicators.
        3. Risks to honeybees are mitigated by prohibiting use on apples and pears and requiring that the end-use product not be applied when bees are actively visiting the treatment area.


        4. A whole hive honeybee study will be conducted following EPA approved protocol.


        5. Confirmatory data will be submitted for freshwater fish, freshwater aquatic invertebrates, and parasitic hymenoptera.


        6. A 30 day toxicity/pathogenicity study of shrimp must be conducted.


        7. Although analyzed batches were acceptable, the submitted manufacturing process did not have sufficient quality control required. Therefore, the Agency is requiring, as a term and condition of the registration, additional quality control procedures. Batches that do not meet the criteria must not be used for commercial production. Detailed requirements are described in Confidential Business Appendix.

          8. Before this manufacturing process can be changed, adequate storage stability data must be provided to the Agency and approved.

        8. Data listed in Table 4. are required to be completed and submitted within specified time frames, as elaborated in Section VII, Actions Required by Registrant.

        These conditional registrations will automatically expire in two (2) years.

      2. Tolerances for Food Uses and /or exemptions

        3. EPA received a pesticide petition (PF-871) from AgraQuest, Inc., proposing [pursuant to section 408(d) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. section 346a(d)], to amend 40 CFR part 180 by establishing an exemption from the requirement of a tolerance for residues of the microbial pesticide, Bacillus subtilis strain QST 713, on growing crops.

        EPA is issuing a notice establishing an exemption from the requirements of a tolerance for residues of Bacillus subtilis strain QST 713 in or on all food commodities.

      3. CODEX Harmonization

        4. There are no CODEX values for Bacillus subtilis strain QST 713.

      4. Risk Mitigation

        5. To mitigate any risk to pesticide handlers and applicators, standard personal protective equipment are required including: long sleeved shirt and long pants; waterproof gloves; shoes plus socks; dust/mist filtering respirator (MSHA/NIOSH approval number prefix TC-21C), or a NIOSH approved respirator with any N, P, R, or HE filter; and a Restricted-entry Interval (REI) of 4 hours are required to mitigate occupational exposure and risk to pesticide handlers.

        To mitigate risk to bees, the registration is limited to two years, apples and pears are not allowed as use sites, and labeling to prevent application when bees are actively visiting the treatment area is required.

      5. Endangered Species Statement

        6. We note that 3 aquatic amphipods are currently listed as endangered. They are the Hay's Spring Amphipod (likely to occur in the District of Columbia), the Illinois Cave Amphipod (likely to occur in Monroe County, Illinois), and the Peck's Cave Amphipod (likely to occur in Comal County, Texas). However, none of these are expected to be impacted by the terrestrial use of QST -713 strain of B. subtilis because this strain has not been identified as a pathogen to amphipods and any exposure would be extremely limited .

    3. Labeling Rationale



      1. Human Health Hazard (WPS and non-WPS)

        2. Bacillus subtilis strain QST 713 products with commercial use sites are subject to the Worker Protection Standard. Because of the low toxicity of Bacillus subtilis strain QST 713 , the Re-Entry Interval for uses within the scope of WPS is 4 hours. Precautionary statements and personal protective equipment as specified below are required based on the acute toxicity categories of this organism.

      2. Environmental Hazard

        3. Precautionary labeling is required as indicated below.

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  8. Actions Required by Registratns

    1. Precautionary Labeling

      2. Bacillus subtilis strain QST 713 products must state the following under the heading "Precautionary Statements":

      Personal Protective Equipment required for Applicators and other handlers must wear:

      Long sleeved shirt and long pants. Waterproof gloves. Shoes plus socks. Dust/mist filtering respirator (MSHA/NIOSH approval number prefix TC-21C), or a NIOSH approved respirator with any N, P, R, or HE filter.

      WPS labels must state the following under the heading "User Safety Recommendations"

      Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the toilet.

      Users should remove clothing immediately if pesticide gets inside. Then wash thoroughly and put on clean clothing.

      Users should remove PPE immediately after handling this product. If gloves are worn, wash the outside of gloves before removing. As soon as possible, wash thoroughly and change into clean clothing.

    2. Environmental Hazards Labeling

      3. Provided the following statements are placed into the environmental hazards statement, the risk of Bacillus subtilis strain QST 713 is minimal to nonexistent to non-target organisms including endangered species.



      1. End-Use Product Environmental Hazards Labeling

        2. " Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark. Do not contaminate water by cleaning of equipment or disposal of equipment washwaters. "  and

        " Do not apply this product or allow it to drift to blooming crops or weeds while bees are actively visiting the treatment area."

      2. Manufacturing-Use Product Environmental Hazards Labeling

        3. "Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or public water unless this product is specifically identified and addressed in an NPDES permit. Do not discharge effluent containing this product to sewer systems without previously notifying the sewage treatment plant authority. For guidance, contact your State Water Board or Regional Office of the EPA."

      3. Application Rate

        4. It is the Agency's position that the labeling for the pesticide products containing Bacillus subtilis strain QST 713 as the active ingredient complies with the current pesticide labeling requirements. The Agency has not required a maximum number of applications per season of this active ingredient. However the maximum application rate is 10 lbs/acre.

    3. Labeling

      4. The attached label for Serenade Biofungicide Wettable Powder and QST 713 Technical conform with the labeling requirements for Bacillus subtilis strain QST 713. Some of the essential label requirements are highlighted below.

      The attached label for Serenade Biofungicide Wettable Powder and QST 713 Technical conform with the labeling requirements for Bacillus subtilis strain QST 713. Some of the essential label requirements are highlighted below.

      • Ingredient Statement
      • Registration Number
      • "Keep Out of Reach of Children"
      • Signal Word (CAUTION)
      • Personal Protective Equipment (PPE) Requirements
      • Environmental Hazard Statement
      • Storage and Disposal Statement
      • Agricultural Use Requirements
      • Directions for Use

    4. Data Necessary to Support a Conditional Registration

      5. The data required to fulfill the data gaps are discussed below and the time frames for submission summarized in Table 4.

       
      Table 4: Summary of Conditional Registration Data Requirements
      Product Chemistry Data Required
      Guideline Title of Study Data Required Date Due
      153-9 *885.2400 Storage Stability Data for the 12 month storage stability of the end-use product has not been submitted. This data, along with clarification/justification of the plating technique description described in MRID# 4446517-03 and 446519-03 should be provided. 2 years from date of registration
      151-11 *885.1200 Manufacturing Process Additional data are required to upgrade submitted process, MRID# 446519-04 to acceptable. 1 year from date of registration
      151-11 *885.1200 Manufacturing Process Additional data must be provided to address deficiencies noted in MRID# 448923-01 and 448944-01. 75 days from date of registration
      Ecological Effects Data Required
      154 19 *885-4200 Freshwater Fish toxicity/pathogenicity

      		 MRID 448848-01 - did not meet guideline requirements. A new study must be submitted. 1 year from date of registration
      154-20 *885-4240 Freshwater aquatic invertebrate toxicity/pathogenicity Confirmatory 21 day Freshwater Aquatic Invertebrate Study must be performed. Attenuated and filter sterilized controls should be used in the test. Test lab should attempt to determine cause of death and whether pathogenicity involved. 1 year from date of registration
      154-21 *885-4280 30 Day Toxicity/Pathogenicity in Paleomonetes vulgaris (shrimp) Required due to report of disease in terrestrial amphipod crustacean associated with B. subtilis infection. Protocol must be submitted before initiating study. 1 year from date of registration
      154-23 *885-4340 Non-target insect-parasitic Hymenoptera Confirmatory data on potential pathogenicity based on a new 30 day study must be submitted. 1 year from date of registration
      154-24 *885-4380 Honey bee Dietary toxicity/pathogenicity A 30 day whole hive study is necessary to support a non-expiring registration. The study must follow the EPA approved protocol. 1 year from date of registration
      *885-xxxx = OPPTS Microbial Pesticide Test Guideline Numbers.

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  9. Bibliography

    10. 44651701 Bellet, E. (1998) Product Chemistry for Serenade WP. Unpublished study prepared by Chemical Consultants International, Inc. 4 p.

    44651702 Gingras, B. (1998) Lot Characterization of QST 713 Strain of Dried Bacillus subtilis with Residual Fermentation Media Identified as QST 713 WP: Lab Project Number: L08726SN8: L08726. Unpublished study prepared by IIT Research Institute. 21 p.

    44651703 Gingras, B. (1998) Storage Stability of QST 713 Strain of Dried Bacillus subtilis with Residual Fermentation Media Identified as QST 713 WP: (Interim Report): Lab Project Number: L08726SN9. Unpublished study prepared by IIT Research Institute. 20 p.

    44651704 Bellet, E. (1998) Manufacturing and Analytical Data for Serenade WP. Unpublished study prepared by Chemical Consultants International, Inc. 56 p.

    44651705 Douds, G. (1998) An Acute Whole-Body Inhalation Toxicity Study in Rats with QST 713 WP: Lab Project Number 3474.1. Unpublished Study prepared by Springborn Laboratories, Inc. 48 p.

    44651901 Bellet, E. (1998) Product Chemistry for QST 713 Technical. Unpublished study prepared by Chemical Consultants International, Inc. 4 p.

    44651902 Gringas, B. (1998) Lot Characterization of Bacillus subtilis Strain QST 713: Lab Project Number: L08726SN1. Unpublished study prepared by IIT Research Institute. 22 p.

    44651903 Gringas, B.(1998) Storage Stability of Technical QST 713: (Interim Report): Lab Project Number: L08726SN2. Unpublished study prepared by IIT Research Institute. 18 p.

    44651904 Bellet, E. (1998) Manufacturing and Analytical Data for Technical QST 713. Unpublished study prepared by Chemical Consultants International, Inc. 48 p.

    44651905 Gingras, B. (1998) Sensitivity of Detection of Bacillus subtilis Strain QST 713 for Toxicity/Pathogenicity Testing in Rats: Lab Project Number: L08726SN3. Unpublished study prepared by IIT Research Institute. 30 p. {OPPTS 885.3050}

    44651906 Harrington, K. (1998) Toxicity/Pathogenicity Testing of QST 713 Following Acute Oral Challenge in Rats: Lab Project Number: L08726SN4. Unpublished study prepared by IIT Research Institute. 126 p. {OPPTS 885.3050}

    44651907 Findlay, J. (1998) Acute Dermal Toxicity/Pathogenicity Study of QST 713 in Rabbits: Lab Project Number: L08726SN7. Unpublished study prepared by IIT Research Institute. 27 p. {OPPTS 885.3100}

    44651908 Harrington, K. (1998) Toxicity/Pathogenicity Testing of QST 713 Following Acute Intravenous Challenge in Rats: Lab Project Number: L08726SN5. Unpublished study prepared by IIT Research Institute. 119 p.

    44651909 Harrington, K. (1998) Toxicity/Pathogenicity Testing of QST 713 Following Acute Intratracheal Challenge in Rats: Lab Project Number: L08726SN6. Unpublished study prepared by IIT Research Institute. 137 p.

    44651910 Foster, J.; Grimes, J.; Beavers, J. (1998) An Avian Oral Pathogenicity and Toxicity Study in the Northern Bobwhite: (QST 713): Lab Project Number: 489-101. Unpublished study prepared by Wildlife International Ltd. 28 p. {OPPTS 885.4050}

    44651911 Drottar, K.; Krueger, H. (1998) A Five-Concentration Toxicity and Pathogenicity Test with the Rainbow Trout (Oncorhynchus mykiss): (QST 713): Final Report: Lab Project Number: 489A-101: 489-103. Unpublished study prepared by Wildlife International Ltd. 36 p. {OPPTS 885.4200}

    44651912 Drottar, K.; Krueger, H. (1998) A 48-Hour Static Acute Toxicity Test with the Cladoceran (Daphnia Magna): (QST 713): Final Report: Lab Project Number: 489A-103. Unpublished study prepared by Wildlife International Ltd. 22 p.

    44651913 Drottar, K.; Krueger, H. (1998) A 21-Day Life Cycle Toxicity and Pathogenicity Test with the Cladoceran (Daphnia Magna): (QST 713): Final Report: Lab Project Number: 489A-102B. Unpublished study prepared by Wildlife International Ltd. 41 p. {OPPTS 885.4240}

    44651914 Hoxter, K.; Krueger, H.; Palmer, S. (1998) A Dietary Pathogenicity Toxicity Study with the Parasitic Hymenoptera (Nasonia vitripennis): (QST 713): Lab Project Number: 489-105A. Unpublished study prepared by Wildlife International Ltd. 21 p. {OPPTS 885.4340}

    44651915 Hoxter, K.; Krueger, H.; Palmer, S. (1998) A Dietary Pathogenicity Toxicity Study with the Ladybird Beetle (Hippodamia convergens): (QST 713): Lab Project Number: 489-103B. Unpublished study prepared by Wildlife International Ltd. 24 p. {OPPTS 885.4340}

    44651916 Hoxter, K.; Krueger, H.; Palmer, S. (1998) A Dietary Pathogenicity Toxicity Study with the Green Lacewing Larvae (Chrysoperia carnea): (QST 713): Lab Project Number: 489-104. Unpublished study prepared by Wildlife International Ltd. 17 p. {OPPTS 885.4340}

    44651917 Hoxter, K.; Krueger, H.; Palmer, S. (1998) A Dietary Pathogenicity Toxicity Study with the Honey Bee (Apis mellifera): (QST 713): Lab Project Number: 489-102C. Unpublished study prepared by Wildlife International Ltd. 22 p. {OPPTS 885.4380}

    44664506 Mallory, V. (1998) Primary Eye Irritation in Rabbits with QST 713 TP: Final Report: Lab Project Number: 0421X54.004. Unpublished study prepared by Chrysalis. 28 p.

    44664507 Mallory, V. (1998) Primary Dermal Irritation in Rabbits with QST 713 TP: Final Report: Lab Project Number: 0420XA54.004. Unpublished study prepared by Chrysalis. 25 p.

    44664601 Mallory, V. (1998) Primary Dermal Irritation in Rabbits with QST 713 TP: Final Report: Lab Project Number: 0420XA54.004. Unpublished study prepared by Chrysalis. 16 p.

    44664602 Mallory, V. (1998) Primary Eye Irritation in Rabbits with QST 713 TP: Final Report: Lab Project Number: 0421XA54.004. Unpublished study prepared by Chrysalis. 16 p.

    44664701 Mallory, V. (1998) Acute Oral Exposure Toxicity Study in Rats with QST 713 WP: Final Report: Lab Project Number: 0402XA54.001. Unpublished study prepared by Chrysalis. 26 p.

    44664703 Mallory, V. (1998) Primary Dermal Irritation in Rabbits with QST 713 WP: Final Report: Lab Project Number: 0420XA54.003. Unpublished study prepared by Chrysalis. 26 p.

    44664704 Mallory, V. (1998) Primary Eye Irritation in Rabbits with QST 713 WP: Final Report: Lab Project Number: 0421XA54.003. Unpublished study prepared by Chrysalis. 30 p.

    44664705 Mallory, V. (1998) Delayed Contact Hypersensitivity in Guinea Pigs with QST 713 WP: (Buehler Method): Final Report: Lab Project Number: 0424XA54.001. Unpublished study prepared by Chrysalis. 40 p.

    44884801 Drottar, K.; Krueger, H. (1999) Bacillus subtilis: A Five-Concentration Toxicity and Pathogenicity Test with the Rainbow Trout (Oncorhynchus mykiss): Final Report: Lab Project Number: 498A-101. Unpublished study prepared by Wildlife International Ltd. 38 p. {OPPTS 885.4200}

    44892301 Bellet, E. (1999) Manufacturing and Analytical Data for Serenade WP. Unpublished study prepared by Chemical Consultants International, Inc. 54 p. {OPPTS 885.1100, 885.1200, 885.1300, 885.1400, 885.1500, 885.1600}

    44894401 Bellet, E. (1999) Manufacturing and Analytical Data for Serenade WP. Unpublished study prepared by Chemical Consultants International, Inc. 57 p. {OPPTS 885.1200, 885.1300, 885.1400, 885.1500}

    44907101 Gingras, B. (1999) Storage Stability of Technical QST 713: Final Report: Lab Project Number: L08726 SN2. Unpublished study prepared by IIT Research Institute. 18 p.

    45084501 Product Identification and Disclosure of Ingredients (OPPTS 885.1100)

    Brannen, PM and Kenney, DS. Kodiak registered - A successful biological-control product for suppression of soil-borne pathogens of cotton. Journal of Industrial and Microbial Biotechnology, Vol. 19, No. 3, pp. 169-171, Sept. 1997.

    Duncan, K.W., The effect on Orchestia hurleyi (Amphipoda: Talitridae) of a whitey disease caused by B. subtilis. New Zealand Journal of Zoology, vol. 8, no. 4, pp. 517-528, 1981.

    Duncan, K.W. 1994. Terrestrial Talitridae (Crustacea: Amphipoda). Fauna of New Zealand 31, 128 pages. (ISSN 0111-5383; no. 31). ISBN 0-4-478-04533-6. 10/7/94)

    Fischer, V. (1999) Efficacy of Serenade Against Fire Blight in Apples

    Gupta, D.K. and M. Vyas. 1989. Efficacy of Bacilllus subtilis against mosquito larvae (Anophelis culicfacies). Zeitschrift fuer Angewandte Zoologie 76 (1):85-91.

    Jacob, A. ; Phillip, BM ; Matthew, MP ; Bacilllus subtilis as a pathogen on Bhindi leafroller, Sylepta derogata (Pyralidae:Lepidoptera) Biological control, India. Journal of Invertebrate Pathology. Sept. 1982. V. 40 (2) pp. 301-302.

    Kararah, M.A., F.M. Barakat, M.S. Mikhail, and H.M. Fouly. 1985. Pathophysiology in garlic cloves inoculated with Bacillus subtilis and Bacilllus pumilus, and Erwinia carotovora. Egyptian J. Phytopathol. 17(2) : 131-140.

    Pang, L; Close, M.; Noonan, M; Rhodamine WT and B. subtilis transport through an alluvial gravel aquifer. Ground water. Jan/Feb. 1998. V. 36 (1) p. 112-122.

    Sneath, et. al. Eds, Bergey's Manual7 of Systematic Bacteriology Volume 2, P. , Williams & Wilkins, Baltimore, MD, 1986.

    Stanghellini, M.E. and S.L. Rasmussen. 1989. Two new diseases of Salicornia sp. caused by Bacillus subtilis and Macrophomina phaseolina. Annual Meeting of the American Phytopathological Society, Pacific Division, June 20-21, 1989. Phytopathology 79 (8) : 912.

    Yakovleva, L.M., P.V. Derevyankin, and R.I. Gvozdyak. 1990. Bacteriosis in the Norway maple. Mikrobioloicheskii Zhurnal (Kiev) 52 (4) : 60-64.

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