Document ID: EPA-HQ-OPP-2023-0008-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2023-03-24T04:00Z

EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Biopesticides and Pollution Prevention Division contact: Alexandra Boukedes, 202-566-1511

SUBMISSION: Email the completed template to: Boukedes.alexandra@epa.gov.

Danisco US Inc.

1F8927

	EPA has received a pesticide petition (1F8927) from Danisco US Inc, 925 Page Mill Road, Palo Alto, CA 94304 requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish exemptions from the requirement of a tolerance for the microbial pesticides Gluconobacter cerinus strain BC18B and Hanseniaspora uvarum strain BC18Y in or on all food commodities.

Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, Danisco US Inc. has submitted the following summary of information, data, and arguments in support of their pesticide petition. This summary was prepared by Danisco US Inc. and EPA has not fully evaluated the merits of the pesticide petition. The summary may have been edited by EPA if the terminology used was unclear, the summary contained extraneous material, or the summary unintentionally made the reader conclude that the findings reflected EPA's position and not the position of the petitioner.

I. Danisco US Inc. Petition Summary
   
   	1F8927
   
A. Product Name and Proposed Use Practices

	 Gluconobacter cerinus strain BC18B and Hanseniaspora uvarum strain BC18Y are proposed for use as seed treatment, soil application, foliar spray, chemigation or aerial application, and post-harvest use for the purposes of fungal, bacterial, and nematode plant disease suppression and prevention. Gluconobacter cerinus strain BC18B and Hanseniaspora uvarum strain BC18Y are beneficial microorganisms that are used to suppress or control plant diseases by improving plant health and via a combination of antibiosis, competition for niches and nutrients, as well as induction of the plant's resistance through systemic defense in plants.

B. Product Identity/Chemistry

 Identity of the pesticide and corresponding residues. Gluconobacter cerinus strain BC18B and Hanseniaspora uvarum strain BC18Y
         
	2. Magnitude of residues at the time of harvest and method used to determine the residue. A determination of the magnitude of residues at harvest is not required for residues that are exempt from tolerances.

	3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. An analytical method for residues of this MPCA is not applicable. It is expected that, when used as proposed, Gluconobacter cerinus strain BC18B and Hanseniaspora uvarum strain BC18Y, would not result in residues that are of toxicological concern.

C. Mammalian Toxicological Profile

Acute Oral Toxicity (OCSPP 870.1100): An acute oral toxicity study was conducted with rats to evaluate the potential for a manufacturing-use product containing 4.66 x 10[10] CFU/ml Gluconobacter cerinus strain BC18B and 2.75 x 10[9] CFU/ml Hanseniaspora uvarum strain BC18Y to cause toxicity following a single oral dose (MRID #51496905). The study was performed using the up-and-down procedure. The median lethal dose (LD50) was determined to be greater than 5,000 mg/kg body weight (Toxicity Category IV).  

Acute Dermal Toxicity (OCSPP 870.1200): The acute dermal toxicity study data requirement was satisfied based on the acute oral toxicity study described above. The acute dermal toxicity of a manufacturing-use product containing 4.66 x 10[10] CFU/ml Gluconobacter cerinus strain BC18B and 2.75 x 10[9] CFU/ml Hanseniaspora uvarum strain BC18Y extrapolated from the acute oral study resulted in an LD50 of greater than 5,000 mg/kg body weight (Toxicity Category IV).

Acute Inhalation Toxicity Study in Rats (OCSPP 870.1300): An acute inhalation toxicity study was conducted with a manufacturing-use product containing 4.66 x 10[10] CFU/ml Gluconobacter cerinus strain BC18B and 2.75 x 10[9] CFU/ml Hanseniaspora uvarum strain BC18Y to evaluate the potential effects of inhalation exposure (MRID #51496906). Under the conditions of the study, a single 4h exposure to acute inhalation of the test substance was greater than 2.13 mg/L in male and female rats (Toxicity Category IV).  

Primary Eye Irritation (OCSPP 870.2400): A primary eye irritation study was conducted with rabbits to evaluate the potential for a manufacturing-use product containing 4.66 x 10[10] CFU/ml Gluconobacter cerinus strain BC18B and 2.75 x 10[9] CFU/ml Hanseniaspora uvarum strain BC18Y to cause irritation following a single ocular exposure (MRID #51496907). The study was performed by instillation of 0.1 ml of the test substance in the conjunctival sac of the right eye of each of 3 rabbits. There was no corneal opacity or iritis in any treated eye during the study. The treated eye of one rabbit had minimal conjunctivitis within 24 hours after exposure that cleared by 48 hours. All animals were free of ocular irritation by 48 hours after exposure. (Toxicity Category IV).  

Primary Dermal Irritation (OCSPP 870.2500): A primary dermal irritation study was conducted with rabbits to evaluate the potential for a manufacturing-use product containing 4.66 x 10[10] CFU/ml Gluconobacter cerinus strain BC18B and 2.75 x 10[9] CFU/ml Hanseniaspora uvarum strain BC18Y, to cause irritation following a single dermal exposure (MRID #51496908). The study was performed by topical application of 0.5 ml of test substance to the skin of three healthy rabbits for 4 hours. After removal of the patches that covered the application sites, one treated site showed very slight erythema. All animals were free of irritation by 24 hours after exposure (Toxicity Category IV).

Acute Pulmonary Toxicity/Pathogenicity Study in Rats (OCSPP 885.3150): An acute pulmonary toxicity/pathogenicity study was conducted with a manufacturing-use product containing Gluconobacter cerinus strain BC18B and Hanseniaspora uvarum strain BC18Y to determine the potential for toxicity and pathogenicity of the microbial pest control agents (MRID #51496909). The test substance was administered to 34 rats (17 male and 17 female) by intratracheal injection in a single high dose of 2.9 x 10[9] viable cells of Gluconobacter cerinus strain BC18B and 2.62 x 10[8] viable cells of Hanseniaspora uvarum strain BC18Y in 0.1 mL. A second group of four rats (2 male and 2 female) remained untreated as controls, and a third group of six rats (3 male and 3 female) received inactivated (autoclaved) test substance. The animals were observed frequently on the day of dosing for mortality and signs of pharmacologic and/or toxicologic effects and once daily thereafter for 23 days. Control groups (untreated and inactive test substance) were conducted concurrently. A gross necropsy of all animals was performed and recorded. Samples of brain, liver, lung, spleen, kidney, lymph nodes, blood and cecum contents were collected from treated rats necropsied on Days 1 (lungs only), 3, 9, 15, and 22/23. Lung samples were collected on the same days as other samples and on day 1. All samples collected were analyzed for viable Gluconobacter cerinus strain BC18B and Hanseniaspora uvarum strain BC18Y CFU content. There were no mortalities attributed to the test substance throughout the study. Clinical observations of irregular respiration were noted for males and females in the inactivated control and for some animals in the active test substance group, which were contributed to the route of administration of the test substance and transient. In all animals, respiration returned to normal by the end of the study. Except for one female in the inactivated control group, which showed mottled lungs on day 23, no findings on gross necropsy were noted for any other animal in any other group. Overall, mean body weights and mean body weight gain for the male and female test group animals were comparable to the control group animals. Gluconobacter cerinus strain BC18B as well as Hanseniaspora uvarum strain BC18Y were either not present or below the limit of detection for all male and female blood, brain, liver, spleen, kidney, and cecum content samples. Both strains were initially detected on day 1 in lung samples and on day 3 in lymph node samples. Clearance was achieved for both strains in lung and lymph node samples by Day 9. Under the conditions of this study, the acute pulmonary administration of Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y, at a dose level of 2.9 x 10[9] and 2.62 x 108 viable CFU/animal, respectively, produced no clinical signs of persistent infection or pathogenicity in treated animals. 

D. Aggregate Exposure

	1. Dietary exposure. Dietary exposure from use of Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y, as proposed according to pre-harvest label directions, is expected to be minimal. The intended use of Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y is application via seed and soil treatment or spray on growing plants for the purpose of disease control and suppression. In addition, both strains are intended to be for disease control or suppression post-harvest. Data in published literature demonstrate that Gluconobacter cerinus is a bacteria and is ubiquitous in soil and on plants and is found in grape musts. This species, together with acetic acid bacteria is used in the food industry for production of food and beverages. Hanseniaspora uvarum is a widespread yeast species frequently isolated from soil, various fruits, and musts. Hanseniaspora uvarum is a predominant yeast species during fermentations of fruit juices and is used in winemaking (see MRID 51496901).

	i. Food. Exposure of Gluconobacter cerinus strain BC18-B and/or Hanseniaspora uvarum strain BC18Y to humans is possible via consumption of food that has been treated post-harvest with these strains. As mentioned above, the species Gluconobacter cerinus strain and Hanseniaspora uvarum are present in or on food and therefore already widely consumed with fruits and beverages. In addition, the results of toxicity testing identify no risk to human health from Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y and both strains do not produce recognized toxins, enzymes, or virulence factors normally associated with mammalian invasiveness or toxicity.

	ii. Drinking water. Exposure to humans from residues of Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y in consumed drinking water would be unlikely. Both strains are not considered for application to surface or ground water. Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y both prefer nutrient-rich environments to grow, which are not expected in drinking water, so significant levels in surface water or ground water are considered improbable. Additionally, the strains are not likely to tolerate the conditions water is subjected to in a drinking water facility. Chlorination, pH adjustments, high temperatures and/or anaerobic conditions of water treatment are expected to inactivate residues of the MPCAs. Significant exposure to Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y from any drinking water source above background is not expected. 

	2. Non-dietary exposure. The potential for non-dietary exposure of the general population, including infants and children to Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y is reasonably low given the primary uses are for agricultural and ornamental treatments, and no residential uses per proposed product label. Personal Protective Equipment (PPE) mitigates the potential for exposure to applicators and handlers of the proposed product when used in agricultural settings.  Label mitigation measures are included on packaging to minimize exposures to the general population including infants and children.  

E. Cumulative Effects

	There is no indication that the microorganisms, Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y, act by a common mechanism of toxicity with other substances to result in any cumulative effects.

F. Safety Determination

	1. U.S. population. Toxicity studies have shown that Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y are not toxic, pathogenic, infective or irritating to mammals following acute exposure. These results indicate the product is not of toxicological concern for the general population when used as proposed on the label.  Further, Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y were not toxic or pathogenic following intratracheal injection, indicating these strains are not of concern for pathogenicity when used as proposed. Based on the data available, there is a reasonable certainty of no harm to the general US population from exposure to Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y.

	2. Infants and children. It is not expected that, when used as proposed, Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y would result in residues that are of toxicological concern. There is a reasonable certainty of no harm for infants and children from exposure to Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y from the proposed uses. Retention of the Food Quality Protection Act (FQPA) safety factor is not necessary as part of the qualitative safety assessment for Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y.  

G. Effects on the Immune and Endocrine Systems

	To date there is no evidence to suggest that Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y function in a manner similar to any known hormone, or that it acts as an endocrine disrupter. 

H. Existing Tolerances

	There is no US EPA tolerance or tolerance exemption for Gluconobacter cerinus strain BC18-B or Hanseniaspora uvarum strain BC18Y.

I. International Tolerances

	A Codex Alimentarium Commission Maximum Residue Level (MRL) is not established for Gluconobacter cerinus strain BC18-B and Hanseniaspora uvarum strain BC18Y.