?/EPA United States Prevention, Pesticides EPA739-R-07-005 Environmental Protection and Toxic Substances September 2007 Agency (7510P) Reregistration Eligibility Decision for BiobanP-1487 ------- UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES CERTIFIED MAIL Dear Registrant: This is to inform you that the Environmental Protection Agency (hereafter referred to as EPA or the Agency) has completed its review of the available data and public comments received related to the preliminary risk assessments for the antimicrobial Bioban P-1487. The Reregi strati on Eligibility Decision (RED) for Bioban P-1487 was approved on September 24, 2007. Public comments and additional data received were considered in this decision. Based on its review, EPA is now publishing its Reregi strati on Eligibility Decision (RED) and risk management decision for Bioban P-1487 and its associated human health and environmental risks. A Notice of Availability will be published in the Federal Register announcing the publication of the RED. The RED and supporting risk assessments for Bioban P-1487 are available to the public in EPA's Pesticide Docket EPA-HQ-OPP-2007-0402 at: www.regulations. gov. The Bioban P-1487 RED was developed through EPA's public participation process, published in the Federal Register on September 10, 2004, which provides opportunities for public involvement in the Agency's pesticide tolerance reassessment and reregi strati on programs. The public participation process encourages robust public involvement starting early and continuing throughout the pesticide risk assessment and risk mitigation decision making process. The public participation process encompasses full, modified, and streamlined versions that enable the Agency to tailor the level of review to the level of refinement of the risk assessments, as well as to the amount of use, risk, public concern, and complexity associated with each pesticide. Using the public participation process, EPA is attaining its strong commitment to both involve the public and meet statutory deadlines. Please note that the Bioban P-1487 risk assessment and the attached RED document concern only this particular pesticide. This RED presents the Agency's conclusions on the dietary, occupational, and ecological risks posed by exposure to Bioban P-1487 alone. This document also contains both generic and product-specific data that the Agency intends to require in Data Call-Ins (DCIs). Note that DCIs, with all pertinent instructions, will be sent to registrants at a later date. Additionally, for product-specific DCIs, the first set of required responses will be due 90 days from the receipt of the DCI letter. The second set of required responses will be due eight months from the receipt of the DCI letter. ------- As part of the RED, the Agency has determined that Bioban P-1487 will be eligible for reregistration provided that all the conditions identified in this document are satisfied, including submission of confirmatory data and labeling changes outlined in Section IV of the document. Sections IV and V of this RED document describe the labeling amendments for end-use products and data requirements necessary for continued registration of Bioban P-1487-containing products. Instructions for registrants on submitting the revised labeling can be found in the set of instructions for product-specific data that accompanies this document. Should a registrant fail to implement any of the requirements outlined in this document, the Agency will have concerns about the risks posed by Bioban P-1487. Where the Agency has identified any unreasonable adverse effect to human health and the environment, the Agency may at any time initiate appropriate regulatory action to address this concern. At that time, any affected person(s) may challenge the Agency's action. If you have questions on this document or the label changes relevant to this reregistration decision, please contact the Chemical Review Manager, Michelle Centra, at (703) 308-2476. For questions about product reregistration and/or the Product DCI that will follow this document, please contact Marshall Swindell at (703)-308-6341. Sincerely, Frank T. Sanders Director, Antimicrobials Division ------- REREGISTRATION ELIGIBILITY DECISION for Bioban P-1487 ListD CASE 3028 Attachment Approved By: Frank T. Sanders Director, Antimicrobials Division September, 24 2007 ------- Table of Contents Bioban P-1487 Reregistration Team 1 Glossary of Terms and Abbreviations 2 Abstract 4 I. Introduction 5 II. Chemical Overview 7 A. Regulatory History 7 B. Chemical Identification 7 C. Use Profile 8 III. Summary of Bioban P-1487 Risk Assessments 10 A. Human Health Risk Assessment 10 1. Toxicity of Bioban P-1487 10 2. FQPA Safety Factor 14 3. Dietary Risk Assessment 15 4. Residential Risk Assessment 15 5. Aggregate Risk Assessment 15 6. Occupational Risk 15 a. Summary of Use Pattern and Formulations 15 b. Occupational Handler Exposure 16 c. Occupational Handler Risk Summary 17 d. Occupational Post-application Exposure 19 e. Occupational Post-application Risk Summary 19 7. Human Incident Data 20 B. Environmental Risk Assessment 20 1. Environmental Fate and Transport 20 a. Bioaccumulation in Aquatic Organisms 21 2. Ecological Risk 21 a. Ecological Toxicity 21 b. Ecological Exposure and Risk 23 c. Risk to Listed Species 23 IV. Risk Management, Reregistration, and Tolerance Reassessment Decision... 25 A. Determination of Reregistration Eligibility 25 B. Public Comments and Responses 25 C. Regulatory Position 26 a. Determination of Safety to U.S. Population 26 b. Determination of Safety to Infants and Children 26 c. Endocrine Disrupter Effects 26 d. Cumulative Risks 27 D. Regulatory Rationale 27 1. Human Health Risk Management 27 ------- 2. Environmental Risk Management 27 3. Other Labeling Requirements 28 4. Listed Species Considerations 28 a. The Endangered Species Act 28 b. General Risk Mitigation 29 V. What Registrants Need to Do 30 A. Manufacturing-Use Products 31 1. Additional Generic Data Requirements 31 2. Labeling for Technical and Manufacturing Use Products 32 B. End-Use Products 32 1. Additional Product-Specific Data Requirements 32 2. Labeling for End-Use Products 32 a. Label Changes Summary Table 33 VI. Appendices 34 A. Table of Use Patterns for Bioban P-1487 35 B. Table of Generic Data Requirements and Studies Used to Make the 36 Reregistration Decision C. Technical Support Documents 40 D. Bibliography Citations 41 E. Generic Data Call-In 45 F. Product Specific Data Call-In 46 G. Batching of End-Use Products 47 H. List of All Registrants Sent the Data Call-In 48 I. List of Available Forms 49 ------- Bioban P-1487 Reregistration Team Health Effects Risk Assessment Jenny Tao Najm Shamim Siroos Mostaghimi Jonathan Chen Timothy McMahon Ecological Risk Assessment David Bays Environmental Fate Risk Assessment Najm Shamim Risk Management Michelle Centra Diane Isbell ------- GLOSSARY OF TERMS AND ABBREVIATIONS a.i. Active Ingredient aPAD Acute Population Adjusted Dose APHIS Animal and Plant Health Inspection Service ARTF Agricultural Re-entry Task Force BCF Bioconcentration Factor CDC Centers for Disease Control CDPR California Department of Pesticide Regulation CFR Code of Federal Regulations ChEI Cholinesterase Inhibition CMBS Carbamate Market Basket Survey cPAD Chronic Population Adjusted Dose CSFII USDA Continuing Surveys for Food Intake by Individuals CWS Community Water System DCI Data Call-In DEEM Dietary Exposure Evaluation Model DL Double layer clothing {i.e., coveralls over SL} DWLOC Drinking Water Level of Comparison EC Emulsifiable Concentrate Formulation EDSP Endocrine Disrupter Screening Program ED STAC Endocrine Disrupter Screening and Testing Advisory Committee EEC Estimated Environmental Concentration. The estimated pesticide concentration in an environment, such as a terrestrial ecosystem. EP End-Use Product EPA U.S. Environmental Protection Agency EXAMS Tier II Surface Water Computer Model FDA Food and Drug Administration FFDCA Federal Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FOB Functional Observation Battery FQPA Food Quality Protection Act FR Federal Register GL With gloves GPS Global Positioning System HIARC Hazard Identification Assessment Review Committee IDFS Incident Data System IGR Insect Growth Regulator IPM Integrated Pest Management RED Reregistration Eligibility Decision LADD Lifetime Average Daily Dose LC50 Median Lethal Concentration. Statistically derived concentration of a substance expected to cause death in 50% of test animals, usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm. LCO Lawn Care Operator LD50 Median Lethal Dose. Statistically derived single dose causing death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation), expressed as a weight of substance per unit weight of animal, e.g., mg/kg. LOAEC Lowest Observed Adverse Effect Concentration LOAEL Lowest Observed Adverse Effect Level LOG Level of Concern LOEC Lowest Observed Effect Concentration mg/kg/day Milligram Per Kilogram Per Day MOE Margin of Exposure MP Manufacturing-Use Product MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted. MRL Maximum Residue Level ------- N/A Not Applicable NASS National Agricultural Statistical Service NAWQA USGS National Water Quality Assessment NG No Gloves NMFS National Marine Fisheries Service NOAEC No Observed Adverse Effect Concentration NOAEL No Observed Adverse Effect Level NPIC National Pesticide Information Center NR No respirator OP Organophosphorus OPP EPA Office of Pesticide Programs ORETF Outdoor Residential Exposure Task Force PAD Population Adjusted Dose PCA Percent Crop Area PDCI Product Specific Data Call-In PDF USDA Pesticide Data Program PF10 Protection factor 10 respirator PF5 Protection factor 5 respirator PHED Pesticide Handler's Exposure Data PHI Pre-harvest Interval ppb Parts Per Billion PPE Personal Protective Equipment PRZM Pesticide Root Zone Model RBC Red Blood Cell RED Reregistration Eligibility Decision REI Restricted Entry Interval RfD Reference Dose RPA Reasonable and Prudent Alternatives RPM Reasonable and Prudent Measures RQ Risk Quotient RTU (Ready-to-use) RUP Restricted Use Pesticide SCI-GROW Tier I Ground Water Computer Model SF Safety Factor SL Single layer clothing SLN Special Local Need (Registrations Under Section 24C of FIFRA) STORET Storage and Retrieval TEP Typical End-Use Product TGAI Technical Grade Active Ingredient TRAC Tolerance Reassessment Advisory Committee TTRS Transferable Turf Residues UF Uncertainty Factor USDA United States Department of Agriculture USFWS United States Fish and Wildlife Service USGS United States Geological Survey WP S Worker Protection Standard ------- ABSTRACT The Environmental Protection Agency (EPA or the Agency) has completed the human health and environmental risk assessments for Bioban P-1487 and is issuing its risk management decision. The risk assessments are based on review of the target database supporting the use patterns of currently registered products and additional information received through the public docket. After considering the revised risk assessments, comments received, and suggestions from interested parties, the Agency developed its risk management decision for uses of Bioban P-1487. As a result of this review, EPA has determined that Bioban P-1487-containing products are eligible for reregi strati on, provided that confirmatory data are submitted to the Agency and labels are amended accordingly. That decision is discussed fully in this document. ------- I. Introduction The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988 to accelerate the reregistration of products with active ingredients registered prior to November 1, 1984 and amended again by the Pesticide Registration Improvement Act of 2003 to set time frames for the issuance of Reregistration Eligibility Decisions. The amended Act calls for the development and submission of data to support the reregistration of an active ingredient, as well as a review of all submitted data by the U.S. Environmental Protection Agency (EPA or the Agency). Reregistration involves a thorough review of the scientific database underlying a pesticide's registration. The purpose of the Agency's review is to reassess the potential hazards arising from the currently registered uses of the pesticide; to determine the need for additional data on health and environmental effects; and to determine whether or not the pesticide meets the "no unreasonable adverse effects" criteria of FIFRA. This document presents the EPA decision regarding the reregistration eligibility of the registered uses of Bioban P-1487. There are two active ingredients in the Bioban P-1487: 4-(2- nitrobutyl) morpholine (PC Code 100801); and 4,4'-(2-ethyl-2-nitromethylene) dimorpholine or 4,4'-(2-ethyl-2-nitro-l,3-propanediyl) bis (PC Code 100802). Bioban P-1487, a mixture of the two active ingredients 4-(2-nitrobutyl) morpholine and 4,4'-(2-ethyl-2-nitromethylene) dimorpholine, is registered for indoor use as a materials preservative and as a microbial growth inhibitor of slime-forming fungi and bacteria. For inhibition of microorganism growth, Bioban P-1487 is applied to various sites, including industrial processes and water systems such as metalworking fluids; oil storage tank bottom water, fuel storage tank bottom water; and to diesel oil, fuel oil, gasoline, and kerosene, as a hydrocarbon preservative. As a materials preservative, Bioban P-1487 is formulated into products such as metal die cast lubricants, corrosion inhibiting metal coatings, mold-release agents (for the manufacture of plastics), and fuel conditioners (for diesel engines). It is not registered for any direct or indirect food uses. Therefore, tolerances have not been established for Bioban P-1487. The Agency has determined that analysis of the potential need for a special hazard-based safety factor under the FQPA is not needed at this time. The Agency does not anticipate dietary, drinking water or residential exposures based on the registered use patterns. Therefore, an FQPA hazard analysis is not necessary at this time. The risks summarized in this document reflect only the registered uses of the active ingredient, Bioban P-1487. The Food Quality Protection Act (FQPA) requires that the Agency consider available information concerning the cumulative effects of a particular pesticide's residues and other substances that have a common mechanism of toxicity. The reason for consideration of other substances is due to the possibility that low-level exposures to multiple chemical substances that cause a common toxic effect by a common toxic mechanism could lead to the same adverse health effect that would occur at a higher level of exposure to any of the substances individually. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for Bioban P-1487 and any other substances. Bioban P-1487 does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, ------- therefore, EPA has not assumed that Bioban P-1487 has a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative. This document presents the Agency's decision regarding the reregi strati on eligibility of the registered uses of Bioban P-1487. In an effort to simplify the RED, the information presented herein is summarized from more detailed information which can be found in the technical supporting documents for Bioban P-1487 referenced in this RED. The revised risk assessments and related addenda are not included in this document, but are available in the Public Docket at http://www.regulations.gov (Docket ID #EPA-HQ-OPP-2007-0402). This document consists of six sections. Section I is the introduction. Section II provides a chemical overview, a profile of the use and usage of Bioban P-1487 and its regulatory history. Section III, Summary of Bioban P-1487 Risk Assessments, gives an overview of the human health and environmental assessments, based on the data available to the Agency. Section IV, Risk Management, Reregi strati on, and Tolerance Reassessment Decision, presents the reregi strati on eligibility and risk management decisions. Section V, What Registrants Need to Do, summarizes the necessary label changes based on the risk mitigation measures outlined in Section IV. Finally, the Appendices list all use patterns eligible for reregi strati on, bibliographic information, related documents and how to access them, and Data Call-In (DCI) information. ------- II. Chemical Overview A. Regulatory History The first product containing Bioban P-1487 was registered on June 7, 1972. Currently, Bioban P-1487 consists of a mixture of two active ingredients: compound I: 4-(2-nitrobutyl) morpholine and compound II: 4,4'-(2-ethyl-2-nitromethylene) dimorpholine. This reregi strati on case therefore, consists of two active EPA PC codes: 100801 assigned to compound I and 100802 assigned to compound II. There are currently four antimicrobial products containing the Bioban P-1487 mixture of both active ingredients that are registered under Section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). B. Chemical Identification 1. Chemical Identity of Bioban P-1487: Chemical Name: Chemical Family: Common/Trade Name: CAS Number: Molecular Formula: Chemical Structures: Compound I: 4-(2-nitrobutyl) morpholine (PC Code 100801) Compound II: 4,4'-(2-ethyl-2-nitromethylene) dimorpholine or 4,4'-(2-ethyl-2-nitro-l,3-propanediyl) bis (PC Code 100802) Morpholines Bioban P-1487 (Compound I + Compound II) Compound I: morpholine Compound II: dimorpholine Compound I: 2224-44-4 Compound II: 1854-23-5 Compound I: CgHie ^63 Compound II: Ci3H25 N32O4 CH, Compound I Compound II ------- Table 1. Chemical Characteristics for Technical Grade Active Ingredient Bioban 1487 (Compound I + Compound II) P- Physical/Chemical Properties Molecular Weight Color Physical State Odor Melting Point Boiling Point Specific Gravity Solubility Vapor Pressure PH Stability Oxidation/Reduction Octanol-Water Partition Coefficient (Log KOW) Flammability Explodability 475.59 Yellow to Brown (5 Gardner) Liquid Mild fish-like odor characteristic of amines -16.5to28.0°C 99to215°Cat760mmHg 1.075 to 1.077 at 25 °C ll,OOOmg/Lat20°C 45% in Tripropylene glycol methyl ether 50% in Hexylene glycol 50% in Dipropylene glycol methyl ether 50% in Toluene 20 to 43 mm Hg at 90 °C 9.5 to 10.0 Indefinitely stable when stored at room temperature in original container N/A: Product does not contain any oxidizing or reducing agents 0.18 to -0.54 Flash Point: > 160 °F (-55 °C) N/A: Product not explosive N/A = Not applicable C. Use Profile Information on the currently registered uses of Bioban P-1487-containing products and an overview of use sites and application methods follows. The detailed table of uses for Bioban P-1487 products eligible for reregi strati on is contained in Appendix A. Type of Pesticide: Bacteriocide, Fungicide Summary of Use: Antimicrobial products containing Bioban P-1487 as an active ingredient are intended for use in industrial processes and water systems (Use Site VIII), and as a materials preservative for a variety of products (Use Site Category VII). Examples of these uses are listed below. For a detailed use description please refer to Appendix A. ------- Materials Preservatives: Bioban P-1487 is used in metal die cast lubricants, corrosion inhibiting metal coatings, mold-release agents (for the manufacture of plastics), and fuel conditioners (for diesel engines). Industrial Processes and Water Systems: Bioban P-1487 is used in industrial processes and water systems such as metalworking fluids; oil storage tank bottom water, fuel storage tank bottom water; and diesel oil, fuel oil, gasoline, and kerosene, as a hydrocarbon preservative. Target Pests: Deterioration/spoilage bacteria, slime-forming bacteria, slime-forming fungi Formulation Types of Bioban P-1487: Soluble concentrates, ready-to-use solutions Method and Rates of Application: The methods and rates of application for Bioban P-1487-containing products vary greatly depending on use site. Please refer to Appendix A for more detailed application rates for each use site and methods of application. Use Classification: General Use Basic Manufacturers: The Dow Chemical Company ------- III. Summary of Bioban P-1487 Risk Assessments The purpose of this summary is to assist the reader by identifying the key features and findings of these risk assessments and to help the reader better understand the conclusions reached in the assessments. The human health and ecological risk assessment documents and supporting information listed in Appendix C were used to formulate the safety finding and regulatory decision for Bioban P-1487. While the risk assessments and related addenda are not included in this document, they are available from the OPP Public Docket EPA-HQ-OPP-2007- 0402, and may also be accessed from www.regulations.gov. Hard copies of these documents may be found in the OPP public docket. The OPP public docket is located in Room S-4900, One Potomac Yard, 2777 South Crystal Drive, Arlington, VA 22202, and is open Monday through Friday, excluding Federal holidays, from 8:30 a.m. to 4:00 p.m. The Agency's use of human studies in the Bioban P-1487 risk assessment is in accordance with the Agency's Final Rule promulgated on January 26, 2006, related to Protections for Subjects in Human Research, which is codified in 40 CFR Part 26. A. Human Health Risk Assessment 1. Toxicity of Bioban P-1487 A brief overview of the toxicity studies used for determining endpoints in the risk assessment is outlined below in Table 2. Further details on the toxicity of Bioban P-1487 can be found in the "BIOBAN P-1487: Toxicology Disciplinary Chapter for the Issuance of the Reregistration Eligibility Decision (RED) Document," dated September 20, 2007; "BIOBAN P- 1487: Revised Report of the Antimicrobials Division's Toxicology Endpoint Selection Committee (ADTC)," dated June 27, 2007; and "BIOBAN P-1487: Antimicrobials Division's Risk Assessment for Issuance of the Reregistration Eligibility Decision (RED) Document," dated September 20, 2007. These documents are available in the EPA Docket at: http://www.regulations.gov (Docket ID #EPA-HQ-OPP-2007-0402). The Agency has reviewed all toxicity studies submitted to support guideline requirements for Bioban P-1487. Although the toxicological database is limited, it was determined that these data are sufficient to support a registration eligibility decision provided the registrant submits confirmatory toxicity data to support continued registration of Bioban P-1487-containing products. The acute toxicity profile for Bioban P-1487 is presented below in Table 2. Bioban P- 1487 was found to be moderately toxic (Toxicity Category III) by the oral route and severely toxic by the dermal route (Toxicity Category II). The Agency has no adequate inhalation toxicity data for Bioban P-1487. A study utilizing a one-hour exposure was submitted showing significant clinical toxicity (blood in the urine, porphyrin discharge, corneal opacity, and conjunctivitis) in the rat; however, this study was classified as unacceptable for regulatory purposes. Bioban P-1487 was shown to be a severe skin and eye irritant (Toxicity Category II and Toxicity Category I, respectively), as well as a dermal sensitizer. 10 ------- Table 2. Summary of Acute Toxicity Data for Bioban P-1487 Guideline No. 870.1100 870.1200 onr\ i onn 870.2400 870.2500 870.2600 Study Type Acute oral toxicity Acute dermal toxicity Acute inhalation toxicity (Purity not reported) Acute eye irritation Acute dermal irritation Skin sensitization MRID #(s) 43558901 41677602 00094944 41677603 41677604 (duplicate 41810802) MRID 42349201 Ace No. 259676 Results LD50 = 620 mg/kg (M+F); 81% ai LD50 = 420 mg/kg (M+F); 92 % ai Corrosive; 92 % ai Severe irritant; 92 % ai Sensitizer; 90 % ai Toxicity Category III II Unacceptable study I II N/A Notes: LC = Lethal Concentration; LD = Lethal Dose; NA = Not Applicable General Toxicity Observations Dermal reactions (erythema and edema) to Bioban P-1487 were evident at all dose levels tested in a 90-day subchronic dermal toxicity study conducted in rats. The hematocrit was slightly reduced in males as was the white blood cell count in females. Creatinine was reduced in males at all dose levels. Body weight was reduced in both sexes, in the absence of any changes in food consumption. At the high-dose level, acanthosis was observed at the site of skin application, and histological examination showed chronic inflammation of the urinary bladder in both males and females. A developmental toxicity study in rabbits is not available. Other toxicity studies indicate that rabbits appear to be more sensitive to Bioban P-1487 than rats. In the rat developmental toxicity study submitted to the Agency, excessive salivation was observed at the mid- and high-dose levels of Bioban P-1487. Reduced body weight gain (36% and 12% reduction from control, respectively) was observed in maternal animals in the high-and mid- dose groups for the 0-20 day time period. There were no significant adverse effects on fetal body weight, crown-rump length, or external, visceral, or skeletal malformations at any dose tested. At the high-dose level there was a slight reduction in live fetuses per dam, and total implants per dam; however, the incidences of these effects were not significantly different from control. No data are available to assess the chronic toxicity of Bioban P-1487. 11 ------- From the available repeat-dose toxicity study, there was no evidence of neurotoxicity in rats following dermal exposure to Bioban P-1487. Convulsions, catalepsy, and tremors were observed at a single oral dose of 800 mg/kg, but not at doses of 500 mg/kg or below in the acute oral toxicity studies. The Agency concluded that there is no concern for neurotoxicity resulting from exposure to Bioban P-1487 based on the appearance of these clinical signs only at an excessive dose that are not likely to be encountered from the registered uses of this chemical. Carcinogenicity Classification There were no data available to assess the carcinogenic potential of Bioban P-1487; therefore, a determination cannot be made at this time. Mutagenicity Potential Bioban P-1487 was found to be negative for mutagencity in the absence or presence of S9 activation in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537. There was no evidence of chromosome aberration induction in the absence or presence of S9 activation in a chromosome aberration test using Chinese Hamster Ovary cells. Bioban P-1487 did not promote unscheduled DNA synthesis in rat hepatocyte cultures, nor did it induce a significant increase in micronuclei in mouse bone marrow cells in an in vivo mammalian erythrocyte micronucleus test. Therefore, Bioban P-1487 is not mutagenic or genotoxic. The doses and toxicological endpoints selected for the Bioban P-1487 exposure scenarios are summarized in Table 3 below: Table 3. Summary of Toxicological Endpoints for Bioban P-1487 Exposure Scenario Dermal Short-Term (1-30 days) Dermal Intermediate- Term (1-6 months) Dose Used in Risk Assessment, UF LOAEL (dermal) = 30 mg/kg/day NOAEL (systemic) = 300 mg/kg/day Special FQPA SF* and Level of Concern for Risk Assessment MOE = 30 (3x inter-species extrapolation, 3x intra-species variation, 3x for use of a LOAEL value) MOE = 100 (lOx inter-species extrapolation, lOx intra-species variation) Study and Toxicological Effects 90-Day (Dermal) Subchronic Toxicity Study in Rats (MRID 42440001, 41619302) LOAEL = 30 mg/kg/day based on skin irritation (erythema and edema) at all doses tested. 90-Day (Dermal) Subchronic Toxicity Study in Rats (MRID 42440001, 41619302) LOAEL = 1000 mg/kg/day based on decreased body weight, chronic inflammation of the urinary bladder in males and females. 12 ------- Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects Dermal Long-Term (> 6 months) NOAEL (systemic) = 300 mg/kg/day MOE = 300 (lOx inter-species extrapolation, lOx intra-species variation, 3x for use of a subchronic endpoint for the long- term endpoint) 90-Day (Dermal) Subchronic Toxicity Study in Rats (MRID 42440001, 41619302) LOAEL = 1000 mg/kg/day based on decreased body weight, chronic inflammation of the urinary bladder in males and females. Inhalation (All Durations) NOAEL(maternal) = 10 mg/kg/day MOE = 300 (lOx inter-species extrapolation, lOx intra-species variation, 3x for severe adverse effects observed in the acute inhalation toxicity study, the lack of repeat inhalation exposure study, severe skin irritation and dermal sensitization. An additional 10X is used to determine the need for additional data due to the need to use of route extrapolation in the assessment. Developmental Toxicity Study in Rats (MRID 416738801, 41978802) LOAEL = 30 mg/kg/day based on excessive salivation and decreased body weight Carcinogenicity (oral, dermal, inhalation) No carcinogenicity data available for Bioban P-1487. Notes: UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level. Dietary and Incidental Oral Dietary and incidental oral endpoints were not selected for Bioban P-1487 based on the current registered use patterns. Short-, Intermediate- and Long-term Dermal The short-term LOAEL of 30 mg/kg/day is based on skin irritation (erythema and edema) at all doses tested in the 90-day dermal subchronic toxicity study in rats. The target MOE is 30 (3X inter-species extrapolation, 3X intra-species variation, 3X for use of a LOAEL). The target MOE was chosen because the established endpoint is for dermal irritation, not a systemic toxic effect. In addition, dermal irritation is considered a reversible and short-term effect, thus supporting a lOx uncertainty factor (3x for interspecies extrapolation and 3x for intraspecies variation). The additional 3X uncertainty factor has been added since no NOAEL was established in the study chosen to set the endpoint. The intermediate- and long-term dermal NOAEL of 300 mg/kg/day is based on decreased body weight and chronic inflammation of the urinary bladder observed in male and female rats in the 90-day dermal toxicity study. The target MOE for intermediate-term dermal exposures is 100 (10X inter-species extrapolation, 10X intra-species variation). The target MOE, for long- 13 ------- term dermal exposure is 300 (lOx for inter-species extrapolation, lOx for intra-species variation, 3x for use of a sub chronic endpoint for the long-term endpoint). Short- and Intermediate-term Inhalation The short- and intermediate-term inhalation NOAEL is 10 based on excessive salivation and decreased body weight observed at the LOAEL of 30 mg/kg/day in the developmental toxicity study conducted in rats. In the absence of route-specific data, it was conservatively assumed that inhalation absorption is equivalent to oral absorption (100%). The target MOE for Bioban P-1487 is 300 for short-, intermediate-, and long-term durations (lOx for inter-species extrapolation, lOx for intra-species variation, 30x (3X for lack of repeat inhalation exposure data, severe adverse effects observed in the acute inhalation toxicity study, severe skin irritation and dermal sensitization, and 10X use of route-to-route extrapolation). The additional lOx uncertainty factor applied for route-to-route extrapolation is used to determine the need for confirmatory inhalation toxicity data and not for risk management purposes. Endocrine Disruption Potential EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) "may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator may designate." Following recommendations of its Endocrine Disrupter and Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disrupter Screening Program (EDSP). When the appropriate screening and/or testing protocols being considered under the Agency's Endocrine Disrupting Screening Program (EDSP) have been developed, Bioban P- 1487 may be subjected to additional screening and/or testing to better characterize effects related to endocrine disruption. 2. FQPA Safety Factor The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is intended to provide an additional 10-fold safety factor (lOx), to protect for special sensitivity in infants and children to specific pesticide residues in food, drinking water, or residential exposures, or to compensate for an incomplete database. The Agency does not anticipate dietary, drinking water or residential exposures based on the registered use patterns. Therefore, an FQPA hazard analysis is not necessary at this time. 14 ------- 3. Dietary Risk Assessment When conducting the dietary exposure assessment, all applications of a pesticide are assessed for any dietary concerns from direct food contact or indirect migration of the pesticide into foods, fruits and vegetables. None of the currently registered uses of Bioban P-1487 are considered food use and are not likely to result in any indirect food migration of these chemicals into food, fruits or vegetables in residential settings. Further, Bioban -1487 is not used for potable water treatment and effluents containing this chemical are not expected to contact fresh water environments. Therefore, a drinking water exposure assessment was not conducted. Therefore, the Agency did not conduct any dietary exposure assessment for Bioban P-1487 based on existing registered uses. 4. Residential Risk Assessment No products containing Bioban P-1487 are labeled for residential use. Furthermore, occupational use of Bioban P-1487-containing products as a materials preservative in metalworking fluids and fuels is not expected to result in any appreciable exposures in a residential setting. As a result, no residential risk assessment has been conducted. 5. Aggregate Risk Assessment The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic Act (FFDCA, Section 408(b)(2)(A)(ii)) require "that there is a reasonable certainty that no harm will result from aggregate exposure to pesticide chemical residue, including all anticipated dietary exposures and other exposures for which there are reliable information." Aggregate exposure typically includes exposures from food, drinking water, residential uses of a pesticide, and other non-occupational sources of exposure. An aggregate risk assessment was not conducted for Bioban P-1487. There are no dietary or residential uses nor are there any post-application exposures that would occur in a residential setting. 6. Occupational Risk a. Summary of Use Pattern and Formulations Workers can be exposed to a pesticide through mixing, loading, and/or applying a pesticide, or re-entering treated sites. Bioban P-1487 is used as an antimicrobial pesticide (e.g., materials preservative, industrial processes and water systems, hydrocarbon preservation, and metal working fluids). Occupational risk assessed for exposure at the time of application is termed "handler" exposure. Post-application occupational exposures occur when workers re- enter sites treated with a pesticide. Application parameters used in the risk assessment are generally defined by the physical nature of the formulation (e.g., formula and packaging), by the equipment required to deliver the chemical to the use site and by the application rate required to achieve an efficacious dose. 15 ------- Exposure scenarios assessed for the occupational uses of Bioban P-1487 are shown in Table 4. These scenarios were selected to be representative of the majority of uses and provide high-end estimates of dermal, or inhalation exposure to Bioban P-1487. In addition, this table shows the maximum application rate associated with the representative use and the appropriate EPA Registration number for the product label. Table 4. Representative Exposure Scenarios Associated with Occupational Exposures to Bioban P-1487 Representative Use Method of Application Exposure Scenario EPA Registration Number Application Rate Material Preservatives Metalworking fluid Fuel • Liquid pour • Liquid pump • Use of treated metalworking fluid • Liquid pour • Liquid pump ST and IT Handler (worker pouring preservative into fluid being treated): dermal and inhalation ST and IT/LT Machinist: dermal and inhalation ST and IT Handler: dermal and inhalation 464-659 464-678 0.26% a.i. by weight (3000 ppm x 86% a.i.) 0.088% a.i. by weight (1350 ppm x 64.6% a.i.) lit exposure values for liquid pour and pump preservation materials were assumed to be representative of exposure related to the addition of Bioban to hydrocarbon fuels. b. Occupational Handler Exposure Occupational risks for all potentially exposed populations are measured by a Margin of Exposure (MOE), which determines how close the occupational exposure comes to a No Observed Adverse Effect Level (NOAEL) from toxicological studies. In the case of Bioban P- 1487, the target MOE for intermediate-term dermal exposures is 100. The target MOE for short- and intermediate-term inhalation exposures is 300. The Agency evaluated representative occupational handler scenarios using maximum application rates from product labels to determine dermal and inhalation exposures to Bioban P- 1487. The majority of the scenarios were assessed using proprietary Chemical Manufacturers Association (CMA) data to estimate potential risks. However, for the metalworking fluid machinist scenario, the Agency applied the ChemSTEER model. The model is available at www.epa.gov/opptintr/exposure/docs/chemsteer.htm. The "preservation of materials" refers to the scenario of a worker adding the preservative to the material being treated (metalworking fluid, fuel, etc.) through either liquid pour or liquid 16 ------- pump methods. Liquid pour refers to a worker transferring the antimicrobial product from a small container to an open vat. Liquid pump refers to a worker transferring the preservative by connecting/disconnecting a chemical metering pump from a tote or by gravity flow. Risks were assessed for the intermediate-term duration for dermal exposures and short- and intermediate-term durations for inhalation exposures for occupational handlers using the appropriate toxicological endpoints. Short-term dermal exposures were not assessed for occupational uses other than the machinist handling metal working fluids. The dermal irritation via short-term exposures for handlers other than the machinist will be mitigated through the use of personal protective equipment (PPE) as specified on the product labels. For these exposure scenarios, the total MOEs that account for combined exposures via dermal and inhalation routes, were not calculated for occupational use scenarios because the toxicological endpoints for dermal and inhalation exposures differ. For more information on the assumptions and calculations of potential exposure risks of Bioban P-1487 to workers, refer to the "Occupational and Residential Exposure Assessment for the Reregi strati on Eligibility Decision Document for Bioban P-1487," dated September 5, 2007 and the "BIOBAN P-1487: Antimicrobials Division's Risk Assessment for Issuance of the Reregi strati on Eligibility Decision (RED) Document," dated September 20, 2007. c. Occupational Handler Risk Summary The Agency has assessed the potential dermal and inhalation risks to occupational handlers from exposure to Bioban P-1487, including materials preservatives and metalworking fluids in an industrial setting. The calculated intermediate-term dermal and short- and intermediate-term inhalation MOEs are shown in Table 5. All of the dermal MOEs are above the target MOE of 100 and all of the inhalation MOEs are above the target MOE of 300. Therefore the intermediate-term dermal and short- and intermediate-term inhalation exposures are not of concern. 17 ------- Table 5. Short- and Intermediate-Term Exposures and Risks for Occupational Handlers using Bioban P-1487 Exposure Scenario Preservation of Metalworking Fluids Preservation of Hydrocarbons Method of Application Liquid pour Liquid pump Liquid pour Liquid pump Unit Exposure (mg/lb a.i.) Dermal" 0.184 0.312 0.135 0.00629 Inhalation 0.0085 0.00348 0.00346 0.000403 App. Rate 0.26% a.i. by weight 0.26% a.i. by weight 0.088% a.i. by weight 0.088% a.i. by weight Quantity Handled/ Treated per day 2,502 Ibs 2,502 Ibs 16,000 Ibs 160,000 Ibs Absorbed Daily Dose (mg/kg/day)b Dermal IT 0.017 0.029 0.027 0.013 Inhalation ST/IT 0.00079 0.00032 0.00069 0.0008 MOEC Dermal (Target MOE = 100) IT 18,000 10,000 11,000 24,000 Inhalation (Target MOE = 300) ST/IT 13,000 31,000 14,000 12,000 ST = short-term, IT = intermediate-term, N/A= No data available, NC = Not conducted a All dermal unit exposure estimates used for occupational handler scenariosr epresent exposures incurred assuming the use of PPE (at least aj ong-sleeve shirt and long pants plus chemical-resistant gloves), as specified on the product labels. b Absorbed Daily dose (mg/kg/day) = [unit exposure (mg/lb ai) * absorption (1.0 for both inhalation and dermal) * application rate * quantity treated / body weight (70 kg). c MOE = NOAEL (mg/kg/day) / Absorbed Daily Dose [Wherem^e rmediate-term NOAEL = 300 mg/kg/day for dermal exposure and the short-term and immediate term NOAEL = 10 mg/kg/day for inhalation exposure. 18 ------- d. Occupational Post-application Exposure Occupational post-application exposures occur from handling or using treated end products. Screening-level assessments were conducted for intermediate-and long-term inhalation exposure for workers handling treated products. These risk estimates were developed using Occupational Safety and Health Administration's (OSHA) Permissible Exposure Limit (PEL) for oil mist. For more information on the assumptions and calculations of potential exposure risks of Bioban P-1487 to workers, refer to the "Occupational and Residential Exposure Assessment for the Reregi strati on Eligibility Decision Document for Bioban P-1487," dated September 5, 2007 and the "BIOBAN P-1487: Antimicrobials Division's Risk Assessment for Issuance of the Reregi strati on Eligibility Decision (RED) Document," dated September 20, 2007. e. Occupational Post-application Risk Summary Table 6 shows the dermal doses and resulting MOEs for a machinist working with metalworking fluids. The short-term dermal exposure is not of concern because the MOE of 65 is above the target MOE of 30. The intermediate- and long-term MOE value of 5,500 is above the respective target MOEs of 100 for intermediate-term, and 300 for long-term exposures. Therefore, the intermediate- and long-term dermal exposures are not of concern. Table 6. Short- Intermediate-, and Long-term Dermal Exposures and Risks for Machinist Exposure to Metalworking Fluids Exposure Scenario Machinist - two hand immersion Percent Active Ingredient 0.258% Exposure Duration ST IT/LT Hand Surface Area (cm2) N/A 840 Film thickness (mg/cm2) 10.3 1.75 Frequency (event/day) N/A 1 Exposure a 2.7E-02 5.4E-02 Dermal MOE (Target MOE is 30 for ST, 100 for IT, and 300 for LT) b 65 5,500 a For ST, exposures are calculated as a.i. per area of skin exposed (mg/cm ) = (% active ingredient x film thickness (10.3 mg/cm2). For IT/LT, exposures are calculated as an Absorbed Daily Dose normalized to body weight (mg/kg/day) = [(% active ingredient x surface area of hands x film thickness (1.75 mg/cm2) x Frequency (event/day)] / Body weight (70 kg). b MOE = NOAEL (mg/kg/day) / exposure, where exposure is a.i. per skin area (mg/cm2) for ST and Absorbed Daily Dose (mg/kg/day) for IT/LT. [Where: ST LOAEL = [(30mg/kg/day X 0.231 kg (rat average body weight M/F)/4 cm2] =1.77 mg/cm2', where 4 cm2 is the rat surface area used to apply the chemical and IT/LT NOAEL = 300 mg/kg/day for dermal exposures]. Table 7 shows the short- and intermediate-term inhalation doses and resulting MOEs for a machinist working with end products treated with Bioban P-1487 metalworking fluids. The inhalation MOE for short-, intermediate-, and long-term exposures to Bioban is above the target MOE of 300; therefore post-application inhalation exposure from metalworking fluids is not a concern. 19 ------- Table 7. Inhalation Post-Application Exposures and Risks Exposure Scenario Machinist Percent Active Ingredient 0.258% OSHA PEL (mg/m3) 5 Inhalation rate (m3/hr) 1.25 Exposure Duration (hrs/day) 8 ST/IT/LT Absorbed Daily Dose" (mg/kg/day) 1.8E-03 ST/IT/LT Inhalation MOE (Target MOE is 300) b 5,400 a Absorbed daily dose (mg/kg/day) = % active ingredient * OSHA PEL (mg/m3) * Inhalation rate (nrVhr) exposure duration (hr/day) / body weight (70 kg). b MOE = NOAEL (mg/kg/day) / absorbed daily dose (mg/kg/day) [Where: ST/IT/LT NOAEL = 10 mg/kg/day for inhalation exposures]. 7. Human Incident Data The Agency reviewed available sources of human incident data for incidents relevant to Bioban P-1487. EPA consulted the following sources of information for human poisoning incidents related to Bioban P-1487 use: (1) OPP Incident Data System (IDS) - The Office of Pesticide Programs (OPP) Incident Data System contains reports of incidents from various sources, including registrants, other federal and state health and environmental agencies and individual consumers, submitted to OPP since 1992; (2) California Department of Pesticide Regulation (1982-2004) - The California Department of Pesticide Regulation pesticide poisoning surveillance program consists of reports from physicians of illness suspected of being related to pesticide exposure since 1982; (3) National Pesticide Information Center (NPIC) - NPIC is a toll-free information service supported by OPP that provides a ranking of the top 200 active ingredients for which telephone calls were received during calendar years 1984-1991; (4) National Poison Control Centers (PCC) (1993 - 1996); and (5) Published Scientific Literature on Incidents. In the data available to the Agency, no reports of serious illness have been associated with human exposure to Bioban P-1487. B. Environmental Risk Assessment A summary of the Agency's environmental fate and risk assessment of Bioban P-1487 is presented below. The uses of Bioban P-1487 are considered indoor uses and were not assessed as the Agency does not anticipate environmental exposure. For a detailed discussion of all aspects of the environmental risk assessment, refer to the Environmental Risk Assessment in the "Bioban P-1487 Ecological Hazard and Environmental Risk Assessment Chapter," dated September 20, 2007; and the "Environmental Fate Assessment Bioban P-1487 for the Reregi strati on Eligibility Decision (RED) Document," dated September 20, 2007. 1. Environmental Fate and Transport The Agency has reviewed the available environmental fate studies and reports submitted for Bioban P-1487 to conduct an environmental fate assessment. These data indicate that Bioban P-1487 has a high vapor pressure (16 mm Hg) at room temperature, is highly water soluble, and is not hydrolytically or photolytically stable under abiotic and buffered conditions. In water, the half life of Bioban P-1487 varies depending on pH: 5 (22 hours), 7 (44 hours), and 9 (46 hours). Although Bioban P-1487 does not readily biodegrade 20 ------- in water or soil, it is not likely to contaminate surface or ground water, as it is hydrolytically unstable with half lives of less than two days. Determinations showed that Bioban P-1487 has a log Kow of 1.7 making it unlikely to bind with soils, and therefore mobile in soils. a. Bioaccumulation in Terrestrial and Aquatic Organisms Aquatic metabolism studies indicate that Bioban P-1487 is stable to microbial degradation and bioaccumulation in terrestrial or aquatic organisms is not likely to occur. Therefore, the bioaccumulation potential of Bioban P-1487 is not of concern to the Agency. 2. Ecological Risk Generally, the Agency's ecological risk assessment compares toxicity endpoints from ecological toxicity studies to estimated environmental concentrations based on environmental fate characteristics and pesticide use data. However, the uses of Bioban P-1487 are considered "indoor" or limited use patterns by the Agency. A summary of the submitted data is provided below. a. Ecological Toxicity For the use patterns of Bioban P-1487, avian acute oral toxicity testing [(850.2100), preferably using the bobwhite quail], freshwater fish acute toxicity testing [(850.1075), preferably the rainbow trout], freshwater invertebrate acute toxicity testing (850.1010), and terrestrial and aquatic plant testing are generally needed for the technical grade active ingredient (TGAI) to establish toxicity and to support the registered uses of this chemical. Based on the results of mammalian studies, Bioban P-1487 was shown to be moderately toxic (Toxicity Category III) by the oral route and severely toxic (Toxicity Category II) by the dermal route of exposure. It is severely irritating to the skin and eyes (Toxicity category II and I, respectively), as well as a dermal sensitizer. Bioban P-1487 is also considered to be highly toxic via the inhalation route of exposure (toxicity category I). The results from the avian acute toxicity and dietary studies are summarized in Table 8. These data indicate that Bioban P-1487 is practically non-toxic to both mallard duck and bobwhite quail. All of the submitted avian studies were determined to be supplemental and do not meet guideline requirements. The acute oral LD50 is greater than 100 mg/kg; therefore, no hazard statement for birds is needed on the labels at this time. Table 8. Avian Acute Oral and Subacute Dietary Toxicity for Bioban P-1487 Test and Organism Acute Oral Toxicity LDso Mallard Duck (Anas Results LC5o (mg/L) or LD50 (mg/kg) LD50> 1000 Toxicity Category Practically non-toxic Comments Supplemental study Reference Fink, R. and Beavers, J. 1990 MRID 93055001 21 ------- Test and Organism platyrhynchos) Eight day dietary LCso Bobwhite Quail (Colinus virginianus) Eight day dietary LC50 Mallard Duck (Anas platyrhynchos ) Results LC5o (mg/L) or LD50 (mg/kg) LC50 > 3692 LC50 > 3692 NOEC = 2076 Toxicity Category Practically non-toxic Practically non-toxic Comments Supplemental study Supplemental study Reference Fink, R. and Beavers, J. 1990 MRID 93055002 Fink, R. and Beavers, J. 1990 MRID 93055003 Freshwater fish toxicity studies using the technical grade active ingredient are used to establish potential toxicity to fish. Data are generally needed for only one species when chemical use sites occur in an indoor setting only or the use patterns are limited, as is the case for Bioban P-1487. The preferred test species are rainbow trout (a coldwater fish) or bluegill sunfish (a warm water fish). Two freshwater fish acute toxicity studies were submitted to the Agency. Results of these studies (Table 9) show that the toxicity ranges from 0.75 mg/L to 0.83 mg/L, indicating that Bioban P-1487 is highly toxic to both rainbow trout and bluegill sunfish, respectively. Since the observed toxicity is < 1.0 ppm, product labeling typically must state: "This pesticide is toxic to fish." Table 9. Freshwater Fish Acute Toxicity for Bioban P-1487 Test and Organism Acute Toxicity LCso Rainbow Trout (Onchorynchus mykiss) Acute Toxicity LC50 Bluegill Sunfish (Lepomis macrochirus) Results LC50 (mg/L) LC50 = 0.75 LC50 =0.83 Toxicity Category Highly toxic Highly toxic Comments Core study Core study Reference Griffen, J. and Thompson, C. 1990. MRID 93055005 Griffen, J. and Thompson, C. 1990. MRID 93055004 A freshwater aquatic invertebrate toxicity test (preferably using Daphnia magna or Daphniapulex) conducted with the TGAI is needed to establish the toxicity of a pesticide to aquatic invertebrates. No studies testing the toxicity of Bioban P-1487 to aquatic invertebrates were submitted to the Agency. Terrestrial and aquatic plant testing was conducted to support the registered uses of Bioban P-1487. As shown in Table 10, Bioban P-1487 was toxic to freshwater alga at microgram concentrations. 22 ------- Table 10. Terrestrial and Aquatic Plant Toxicity for Bioban P-1487 Test and Organism 96-hr. Toxicity Test Freshwater Alga (Selenastrum capricornutum) Results (mg/L) EC50 (growth rate) = 0.844 EC50 (% inhibition) = 0.352 EC50 (cell density) = 0.356 NOEC = 0.049 Toxicity Category None given Comments Core Study Reference Kirk, H.D. et al. 2002 MRID 47005504 b. Ecological Exposure and Risk The Agency has evaluated the indoor uses of Bioban P-1487 being considered for reregi strati on. Avian, freshwater and estuarine/marine aquatic organisms and plants are not expected to be exposed to Bioban P-1487 because of the chemical's indoor use pattern. No modeling was conducted because Bioban P-1487 does not have any uses in once-through cooling tower, antifoulant, ballast water or wood treatment. c. Risk to Listed Species Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and andronomus listed species, or the United States Fish and Wildlife Services (FWS) for listed wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species or their designated habitat. Each federal agency is required under the Act to insure that any action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a listed species or result in the destruction or adverse modification of designated critical habitat. To jeopardize the continued existence of a listed species means "to engage in an action that reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of the species." 50 C.F.R. 402.02. To facilitate compliance with the requirements of the Endangered Species Act subsection (a)(2) the Environmental Protection Agency, Office of Pesticide Programs has established procedures to evaluate whether a proposed registration action may directly or indirectly reduce appreciably the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of any listed species (U.S. EPA 2004). After the Agency's screening-level risk assessment is performed, if any of the Agency's Listed Species LOC Criteria are exceeded for either direct or indirect effects, a determination is made to identify if any listed or candidate species may co-occur in the area of the proposed pesticide use. If determined that listed or candidate species may be present in the proposed use areas, further biological assessment is undertaken. The extent to which listed species may be at risk then determines the need for the development of a more comprehensive consultation package as required by the Endangered Species Act. 23 ------- Bioban P-1487 is used indoors to control microbial growth in diesel oil, gasoline, kerosene storage tanks, fuel tanks, resin, latex or other water based emulsions and typically would fall into this category. For certain use categories, the Agency assumes there will be minimal environmental exposure, and only a minimal toxicity data set is required (Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs U.S. Environmental Protection Agency - Endangered and Threatened Species Effects Determinations, 1/23/04, Appendix A, Section IIB, pg.81). Chemicals in these categories therefore do not undergo a full screening-level risk assessment, and are considered to fall under a "no effect" determination. The materials preservative uses of Bioban P-1487 fall into this category. 24 ------- IV. Risk Management, Reregistration, and Tolerance Reassessment Decision A. Determination of Reregistration Eligibility Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of relevant data concerning an active ingredient, whether or not products containing the active ingredient are eligible for reregi strati on. The Agency has previously identified and required the submission of the generic (i.e., active ingredient-specific) data required to support reregi strati on of products containing Bioban P-1487 as an active ingredient. The Agency has completed its review of these generic data and has determined that the data are sufficient to support reregi strati on of all supported products containing Bioban P-1487. The Agency has completed its assessment of the occupational and ecological risks associated with the use of pesticide products containing the active ingredient Bioban P-1487. Based on a review of these data and on public comments on the Agency's assessments for the active ingredient Bioban P-1487, the Agency has sufficient information on the human health and ecological effects of Bioban P-1487 to make decisions as part of the tolerance reassessment process under FFDCA and reregi strati on process under FIFRA, as amended by FQPA. The Agency has determined that Bioban P-1487-containing products are eligible for reregi strati on provided that: (i) current data gaps and confirmatory data needs are addressed; and (ii) label amendments are made as described in Section V. Appendix A summarizes the uses of Bioban P- 1487 that are eligible for reregi strati on. Appendix B identifies the generic data requirements that the Agency reviewed as part of its determination of reregi strati on eligibility of Bioban P-1487 and lists the submitted studies that the Agency found acceptable. Data gaps are identified as generic data requirements that have not been satisfied with acceptable data. Based on its evaluation of Bioban P-1487, the Agency has determined that Bioban P- 1487 products, unless labeled and used as specified in this document, would present risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement the submission of confirmatory data as well as the label changes identified in this document, the Agency may take regulatory action to address this lack of information for Bioban P-1487. If all changes outlined in this document are fully complied with, then no risks of concern exist for the registered uses of Bioban P-1487 and the purposes of this determination. B. Public Comments and Responses Through the Agency's public participation process, the EPA worked with stakeholders and the public to reach the regulatory decision for Bioban P-1487. EPA released its preliminary risk assessment for Bioban P-1487 for public comment on July 6, 2007. The Agency received minimal comments during the 60-day public comment period on the Bioban P-1487 risk assessment and supporting science documents, which closed on September 4, 2007. 25 ------- C. Regulatory Position The Agency has determined that, if confirmatory data are submitted as described in this document and labels are amended to ensure that appropriate PPE is on all product labels, human health risks as a result of exposures to Bioban P-1487 are within acceptable levels. In other words, EPA has concluded that Bioban P-1487 meets FQPA safety standards. In reaching this determination, EPA has considered the available information on the special sensitivity of infants and children, as well as exposures to Bioban P-1487 from all possible sources. a. Determination of Safety to U.S. Population As part of the FQPA tolerance reassessment process, EPA assessed the risks associated with Bioban P-1487. The Agency has determined that Bioban P-1487, with amendments and changes specified in this document, meet the safety standards under the FQPA amendments to section 408(b)(2)(D) of the FFDCA, and that there is a reasonable certainty no harm will result to the general population or any subgroup from the use of Bioban P-1487. In reaching this conclusion, the Agency has considered all available information on the toxicity, use practices and exposure scenarios, and the environmental behavior of Bioban P-1487. b. Determination of Safety to Infants and Children EPA has determined that the currently registered uses of Bioban P-1487, with changes as specified in this document, meet the safety standards under the FQPA amendments to section 408(b)(2)(C) of the FFDCA, that there is a reasonable certainty of no harm for infants and children. The safety determination for infants and children considers the toxicity, use practices, and environmental behavior noted above for the general population, but also takes into account the possibility of increased susceptibility to the toxic effects of Bioban P-1487 residues in this population subgroup. There are no dietary or residential uses nor are there any post-application exposures that would occur in a residential setting. Therefore, an aggregate risk assessment was not conducted for Bioban P-1487. In addition, Bioban -1487 is not used for potable water treatment and effluents containing this chemical are not expected to contact fresh water environments. Therefore, a drinking water exposure assessment was not conducted. c. Endocrine Disrupter Effects EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to determine whether certain substances (including all pesticide active and other ingredients) "may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other endocrine effects as the Administrator may designate." Following recommendations of its Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that EPA include evaluations of potential effects in wildlife. For pesticides, EPA will use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have an effect in humans, FFDCA 26 ------- authority to require the wildlife evaluations. As the science develops and resources allow, screening of additional hormone systems may be added to the Endocrine Disrupter Screening Program (EDSP). When the appropriate screening and/or testing protocols being considered under the EDSP have been developed, Bioban P-1487 may be subject to additional screening and/or testing to better characterize effects related to endocrine disruption. d. Cumulative Risks Risks summarized in this document are those that result only from the use of Bioban P- 1487. The Food Quality Protection Act (FQPA) requires that the Agency consider "available information" concerning the cumulative effects of a particular pesticide's residues and "other substances that have a common mechanism of toxicity." The reason for consideration of other substances is due to the possibility that low-level exposures to multiple chemical substances that cause a common toxic effect by a common toxic mechanism could lead to the same adverse health effect as would a higher level of exposure to any of the substances individually. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for Bioban P-1487. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/. D. Regulatory Rationale The Agency has determined that Bioban is eligible for reregi strati on provided that additional data identified in this RED confirm this decision and label amendments are made to ensure that all labels contain appropriate PPE requirements. Where labeling revisions are warranted, specific language is set forth in the summary tables of Section V of this document. 1. Human Health Risk Management No human health risk mitigation measures are necessary for the antimicrobial use of Bioban P-1487 at this time. Additional data are required to confirm the decisions outlined in this document. The following toxicity study are needed for Bioban P-1487: - Chronic Toxicity/Carcinogenicity Study in Rodents (OPPTS 870.4300). 2. Environmental Risk Management No environmental risk mitigation measures are necessary for the antimicrobial use of Bioban P-1487 at this time. The Agency recognizes that the currently registered uses of Bioban P-1487 are limited to indoors. 27 ------- 3. Other Labeling Requirements In order to be eligible for reregi strati on, various use and safety information will be included in the labeling of all end-use products containing Bioban P-1487. For the specific labeling statements and a list of outstanding data, refer to Section V of this RED document. 4. Listed Species Considerations a. The Endangered Species Act Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and andronomus listed species, or the United States Fish and Wildlife Services (FWS) for listed wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species or their designated habitat. Each federal agency is required under the Act to insure that any action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a listed species or result in the destruction or adverse modification of designated critical habitat. To jeopardize the continued existence of a listed species means "to engage in an action that reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of the species. "50 C.F.R. 402.02. To facilitate compliance with the requirements of the Endangered Species Act subsection (a)(2) the Environmental Protection Agency, Office of Pesticide Programs has established procedures to evaluate whether a proposed registration action may directly or indirectly reduce appreciably the likelihood of both the survival and recovery of a listed species in the wild by reducing the reproduction, numbers, or distribution of any listed species (U.S. EPA 2004). After the Agency's screening-level risk assessment is performed, if any of the Agency's Listed Species LOG Criteria are exceeded for either direct or indirect effects, a determination is made to identify if any listed or candidate species may co-occur in the area of the proposed pesticide use. If determined that listed or candidate species may be present in the proposed use areas, further biological assessment is undertaken. The extent to which listed species may be at risk then determines the need for the development of a more comprehensive consultation package as required by the Endangered Species Act. For certain use categories, the Agency assumes there will be minimal environmental exposure, and only a minimal toxicity data set is required (Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs U.S. Environmental Protection Agency - Endangered and Threatened Species Effects Determinations, 1/23/04, Appendix A, Section IIB, pg.81). Chemicals in these categories therefore do not undergo a full screening-level risk assessment and are considered to fall under a "no effect" determination. The materials preservative uses of Bioban P-1487 fall into this category. 28 ------- b. General Risk Mitigation Bioban P-1487 end-use products (EPs) may also contain other registered pesticides. Although the Agency is not proposing any mitigation measures for products containing Bioban P-1487 specific to federally listed species, the Agency needs to address potential risks from other end-use products. Therefore, the Agency requires that users adopt all listed species risk mitigation measures for all active ingredients in the product. If a product contains multiple active ingredients with conflicting listed species risk mitigation measures, the more stringent measure(s) should be adopted. 29 ------- V. What Registrants Need to Do The Agency has determined that Bioban P-1487 is eligible for reregi strati on provided that: (i) additional data that the Agency intends to require confirm this decision and (ii) label amendments are made. To implement this decision, the registrants must amend their product labeling to incorporate the label statement set forth in the Label Changes Summary Table in Section B below (Table 24). The additional data requirements that the Agency intends to obtain will include, among other things, submission of the following: For Bioban P-1487 technical grade active ingredient products, the registrant needs to submit the following items: Within 90 days from receipt of the generic data call-in (DCI): 1. Completed response forms to the generic DCI (i.e., DCI response form and requirements status and registrant's response form); and 2. Submit any time extension and/or waiver requests with a full written justification. Within the time limit specified in the generic DCI: 1. Cite any existing generic data which address data requirements or submit new generic data responding to the DCI. Please contact Michelle Centra at (703) 308-2476 with questions regarding generic reregi strati on. By US mail: By express or courier service: Document Processing Desk Document Processing Desk Michelle Centra Michelle Centra Office of Pesticide Programs Office of Pesticide Programs (751OP) (751OP) U.S. Environmental Protection Agency U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW One Potomac Yard, Room S-8845 Washington, DC 20460-0001 2777 South Crystal Drive Arlington, VA 22202 For end-use products containing the active ingredient Bioban P-1467, the registrant needs to submit the following items for each product. Within 90 days from the receipt of the product-specific data call-in (PDCI): 1. Completed response forms to the PDCI (i.e., PDCI response form and requirements status and registrant's response form); and 2. Submit any time extension or waiver requests with a full written justification. 30 ------- Within eight months from the receipt of the PDCI: 1. Two copies of the confidential statement of formula (EPA Form 8570-4); 2. A completed original application for reregi strati on (EPA Form 8570-1). Indicate on the form that it is an "application for reregi strati on"; 3. Five copies of the draft label incorporating all label amendments outlined in Table 23 of this document; 4. A completed form certifying compliance with data compensation requirements (EPA Form 8570-34); 5. If applicable, a completed form certifying compliance with cost share offer requirements (EPA Form 8570-32); and 6. The product-specific data responding to the PDCI. Please contact Marshall Swindell at (703) 308-6341 with questions regarding product reregi strati on and/or the PDCI. All materials submitted in response to the PDCI should be addressed as follows: By US mail: By express or courier service: Document Processing Desk Document Processing Desk Marshall Swindell Marshall Swindell Office of Pesticide Programs (751 OP) Office of Pesticide Programs (751 OP) U.S. Environmental Protection Agency U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Room S-4900, One Potomac Yard Washington, DC 20460-0001 2777 South Crystal Drive Arlington, VA 22202 A. Manufacturing Use Products 1. Additional Generic Data Requirements The generic database supporting the reregi strati on of Bioban P-1487 has been reviewed and determined to be substantially complete. However, the following additional data requirements have been identified by the Agency as confirmatory data requirements and are included in the generic data call in (DCI) for this RED. Confirmatory toxicological data must be submitted to fully characterize the following hazards: combined chronic toxi city /carcinogen! city study to assess potential chronic toxi cities as well as define the carcinogenic potential of Bioban P-1487 since there is the potential for long- term exposures due to the metal working fluid use. 31 ------- The following ecological toxicity data must be submitted to fully characterize the invertebrate hazards: acute toxicity to freshwater invertebrates (preferably using Daphnia magna or Daphnia pulex). The requested toxicolgy and ecological study are outlined in Table 11. Table 11. Confirmatory Data Requirements for Bioban P-1487 Guideline Study Name Combined Chronic Toxicity /Carcinogenicity -Rat Acute Freshwater Invertebrate Study1 New OPPTS Guideline Number 870.3800 850.1010 Needed if use patterns are expanded beyond those evaluated in this RED. 2. Labeling for Technical and Manufacturing Use Products To ensure compliance with FIFRA, technical and manufacturing-use product (MP) labeling should be revised to comply with all current EPA regulations, PR Notices and applicable policies. The Technical and MP labeling should bear the labeling contained in Table 12, Label Changes Summary Table. B. End-Use Products 1. Additional Product-Specific Data Requirements Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific data regarding the pesticide after a determination of eligibility has been made. The Registrant must review previous data submissions to ensure that they meet current EPA acceptance criteria and if not, commit to conduct new studies. If a registrant believes that previously submitted data meet current testing standards, then the study MRID numbers should be cited according to the instructions in the Requirement Status and Registrants Response Form provided for each product. A product-specific data call-in will be issued at a later date. 2. Labeling for End-Use Products Labeling changes are necessary to implement measures outlined in Section IV above. Specific language to incorporate these changes is specified in Table 12, Label Changes Summary Table. Registrants may generally distribute and sell products bearing old labels/labeling for 26 months from the date of the issuance of this Reregi strati on Eligibility Decision document. Persons other than the registrant may generally distribute or sell such products for 52 months from the approval of labels reflecting the mitigation described in this RED. However, existing stocks time frames will be established case-by-case, depending on the number of products involved, the number of label changes, and other factors. Refer to "Existing Stocks of Pesticide Products; Statement of Policy," Federal Register, Volume 56, No. 123, June 26, 1991. 32 ------- a. Label Changes Summary Table In order to be eligible for reregi strati on, all product labels must be amended to incorporate the risk mitigation measure outlined in Section IV of the Bioban P-1487 RED.^, e following table describes how language on the labels should be amended. Table 12. Labeling Changes SummaryTah Description Amended Labeling Language Placement on Label Environmental Hazards Statements Required by the RED and Agency Label Policies "This product is toxic to fish and aquatic invertebrates. Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or other waters unless in accordance with the requirements of a National Pollution Discharge Elimination System (NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not discharge effluent containing this product to sewer systems without previously notifying the local sewage treatment plant authority. For guidance contact your State Water Board or Regional Office of the EPA." Precautionary Statements End Use Products Intended for Occupational Use PPE Requirements "Wear a long-sleeve shirt, long pants, shoes, socks, and chemical-resistant gloves." Immediately following/below Precautionary Statements: Hazards to Humans and Domestic Animals 33 ------- VI. APPENDICES 34 ------- Appendix A. Table of Use Patterns for Bioban P-1487 Use Site Formulation/ Reg. No. Method of Application Application Rate/ No. of applications Use Limitations Industrial processes and water systems. Metalworking Fluids Hydrocarbon Preservations 464-674 (Ready-to use) 464-659 (Soluble Concentrate) 464-674 (Ready-to use) 464-678 (Ready-to use) Not Listed Not Listed Add to storage tanks Add to Storage tanks: slug dose or intermittent metering A dose of 1000 to 2000ppm 2500ppm for fouled systems In concentrates: lOOOppm Diluted Fluid: 1000- SOOOppm Maintenance: 100 to 2000ppm at weekly intervals Add 2.2 gallons of product to each 1,000 gallons of water / concentration of lOOOppm 180- 350ppm product to water None Listed None Listed None Listed None Listed Materials preservatives Die Cast Lubricants and mold release agents Diesel fuel Conditioner 464-674 (Ready-to use) 464-665 (Ready-to use) Pour into Fuel tank 1,000 to 2,000ppm for initial treatment 2,500ppm for fouled systems. Entire Contents (12 oz) to 10 - 26 gallon fuel tank None Listed None Listed 35 ------- Appendix B. Table of Generic Data Requirements and Studies Used to Make the Reregistration Decision Guide To Appendix B Appendix B lists the generic (not product specific) data requirements which support the re-registration of Bioban P-1487. These requirements apply to Bioban P-1487 in all products, including data requirements for whicha tech nical grade active ingredient is the test substance. The data table is organized in the following formats: 1. Data Requirement (Columns 1 and 2). The data requirements are listed by Guideline Number. The first column lists the new Part 158 Guideline numbers, and the second column lists the old Part 158 Guideline numbers. Each Guideline Number has an associated test protocol set forth in the Pesticide Assessment Guidance, which are available on the EPA website. 2. Guideline Description (Column 3). Identifies the guideline type. Use Pattern (Column 4). This column indicates the standard Antimicrobial Division use patterns categories for which the generic (not product specific) data requirements apply. The number designations are used in Appendix B. (1) Agricultural premises and equipment (2) Food handling/ storage establishments premises and equipment (3) Commercial, institutional and industrial premises and equipment (4) Residential and public access premises (5) Medical premises and equipment (6) Human water systems (7) Materials preservatives (8) Industrial processes and water systems (9) Antifouling coatings (10) Wood preservatives (11) Swimming pools (12) Aquatic areas 3. Bibliographic Citation (Column 5). If the Agency has data in its files to support a specific generic Guideline requirement, this column will identify each study by a "Master Record Identification (MRID) number. The listed studies are considered "valid" and acceptable for satisfying the Guideline requirement. Refer to the Bibliography appendix for a complete citation of each study. 36 ------- DATA REQUIREMENT New Guideline Number Old Guideline Number Study Title Use Pattern CITATION(S) MRID Number PRODUCT CHEMISTRY 830.1550 830.1600 830.1620 830.1650 830.1670 830.1700 830.1750 830.1800 830.6302 830.6303 830.6304 830.7200 830.7220 830. 7300 830.7840 830.7860 830.7950 830.7000 830.6317 830.6314 830.6315 830.6316 830. 7300 61-1 6 1-2 A 61-2B 62-1 62-2 62-3 63-2 63-3 63-4 63-5 63-6 63-7 63-8 63-9 63-12 63-13 63-14 63-15 63-16 63-7 Product Identity and Composition Starting Materials and Manufacturing Process Formation of Impurities Preliminary Analyses Certification of Limits Analytical Method Color Physical State Odor Melting Point Boiling Point Density Solubility Vapor Pressure PH Stability Oxidation/Reduction: chemical incompatibility Flammability Explodability Density 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980, 41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980,41995101 00034980 00034980 00034980 00034980,41995101 37 ------- DATA REQUIREMENT New Guideline Number 830.7840 830.7860 830.7950 Old Guideline Number 63-8 63-9 Study Title Solubility Vapor Pressure Use Pattern 7,8 7,8 CITATION(S) MRID Number 00034980,41995101 00034980,41995101 ECOLOGICAL EFFECTS 850.2100 850.2200 850.1075 850.1075 850.1010 850.5400 71-1 71-2 72-1 72-1 72-2 123-2 Avian acute oral toxicity test - Mallard/duck Avian dietary toxicity test - Quail Fish acute toxicity test - Bluegill Sunfish Fish acute toxicity - Rainbow Trout Acute Daphnid Study Green algae - Selenastrum capricornutum (Pseudokerscheneria subcapitatum) 7,8 7,8 7,8 7,8 7,8 7,8 93055001 93055002 93055004 93055005 Data Gap 47005504 TOXICOLOGY 870.1100 870.1200 870.1300 870.2400 870.2500 870.2600 870.3250 870.3700 870.4300 870.5100 870.5300 870. 5375 870.5550 870.5385 870.7485 81-1 81-2 81-3 81-4 81-5 81-6 82-3 83-3 83-5 84-2 84-2 84-2 84-2 84-2 85-1 Acute oral toxicity - Rat Acute dermal toxicity - Rabbit Acute inhalation toxicity - Rat Acute eye irritation - Rabbit Acute dermal irritation Skin sensitization 90-Day dermal toxicity Prenatal developmental toxicity study Combined chronic toxicity/carcinogenicity Bacterial reverse mutation test In vitro mammalian cell gene mutation test In vitro mammalian chromosome aberration test Unscheduled DNA synthesis in mammalian cells in culture Mammalian bone marrow chromosomal aberration test Metabolism and pharmacokinetics 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 7,8 43558901 41677602 Data Gap 41677603 41677604, 41810802 00104805 Not needed 41673801, 41978802 Data Gap 41619301 45655301 41298502, 41567901 41298503 47005501, 46965903 Not needed 38 ------- ENVIRONMENTAL FATE 835.2110 835.3110 Non-Guideline 161-1 None Non-Guideline Hydrolysis as a function of pH Ready biodegradability Soil partition co-efficient 7,8 7,8 7,8 43494001 47005502 45900901 39 ------- Appendix C: Technical Support Documents Additional documentation in support of this RED is maintained in the OPP Public Docket EPA- HQ-OPP-2007-0402, and may also be accessed from www.regulations.gov. Hard copies of these documents may be found in the OPP public docket. The OPP public docket is located in Room S-4900, One Potomac Yard, 2777 South Crystal Drive, Arlington, VA 22202, and is open Monday through Friday, excluding Federal holidays, from 8:30 a.m. to 4:00 p.m. All documents, in hard copy form, may be viewed in the OPP docket room or downloaded or viewed via the Internet at the following site: http://www.regulations.gov (EPA- HQ-OPP-2007-0402). These documents include: Risk Assessment and Supporting Science Documents: • Bioban P-1487: Antimicrobials Division's Risk Assessment for Issuance of the Reregistration Eligibility Decision (RED) Document. Case No. 3028, PC Code: 100801, 100802, DP Barcode: 338285. 9/20/07, Jenny Tao, Risk Assessor. • Bioban P-1487: Toxicology Disciplinary Chapter for the Issuance of the Reregistration Eligibility Decision (RED) Document. Case No. 3028, PC Code: 100801, 100802, DP Barcode: 338284. 9/20/07, Jenny Tao, Senior Toxicologist. • BIOBAN P-1487: Revised Report of the Antimicrobials Division's Toxicology Endpoint Selection Committee (ADTC). 6/27/07, Tim McMahon, Ph.D., Chair, ADTC. • Product Chemistry Science Chapter. PC Codes 100801, 100802, Case 3028, Antimicrobials Division, 6/20/07, A. Najm Shamim, Ph.D., Chemist. • DIETARY EXPOSURE ASSESSMENT OF BIOBAN P-1487 FOR REREGISTRATION ELIGIBILITY DECISION Case No. 3028, PC Code: 100801, 100802, DP Barcode: 340643. 6/21/07, A. Najm Shamim, Ph.D. Chemist. • Occupational and Residential Exposure Assessment for Bioban BIOBAN P-1487™ Antimicrobial Agent [4-(2-nitrobutyl)morpholine and 4,4'-(2-ethyl-2- nitrotrimethylene)dimorpholine]. Case No.: 3028, DP Barcode: D338283, 9/5/07, Siroos Mostaghimi, Ph.D., Senior Scientist. • Environmental Fate Risk Assessment of BIOBAN P-1487 for the Reregistration Eligibility Decision (RED) Process. Case No. 3028, PC Code: 100801, 100802, DP Barcode: 340652. 9/20/07, A. Najm Shamim, Ph.D., Chemist. • Environmental Effects Assessment of 4-(2-nitrobutyl) morpholine (Bioban P-1487) for the Reregistration Eligibility Decision (RED) Document. Case No.: 3028, DP Barcode: D340653, 9/20/07, David C. Bays, Microbiologist. 40 ------- Appendix D. Citations Considered to be Part of the Data Base Supporting the Reregistration Decision (Bibliography) MRID Number Citation 00034980 Commercial Solvents Corporation (1969). CSCA(R)IBiocide P-1487. (Unpublished study received Jun 25, 1969 under 271-30; submitted by International Minerals and Chemical Corp., Terre Haute, Ind.; CDL:001945-A). 00094944 Goldenthal, E.I.; Wazeter, F.X.; Dean, W.P. (1973) Acute Inhalation Toxicity Study (LC50) in Albino Rats: 267-009; Report No. PLR-11. (Unpublished study received Jan 14, 1981 under 271-30; prepared by International Research and Development Corp., submitted by International Minerals & Chemical Corp., Terre Haute, Ind.; CDL:244383-F) 00104805 Wilbur, S. (1978) P-1487 Skin Sensitization: SW78/11. (Unpublished study received Apr 25, 1979 under 271-30; submitted by Inter- national Minerals & Chemical Corp., Terre Haute, IN; CDL: 238693-A. 41298502 Desai, L. (1989) Chromosome Aberrations in Chinese Hamster Ovary (CHO) Cells: Bioban P-1487 Antimicrobial Agent: Lab Project Number 89G- 0095. Unpublished study prepared by Toxikon Corp. 15 p. 41298503 Desai, L. (1989) Unscheduled DNA Synthesis in Rat Liver Primary Cell Cultures: Bioban P-1487 Antimicrobial Agent: Lab Project Number 89G-0094. Unpublished study prepared by Toxikon Corp. 12 p. 41567901 Desai, L. (1989) Chromosome Aberration in Chinese Hamster Ovary (CHO) Cells: Lab Project Number: 89G-0095. Unpublished study prepared by Toxikon Corp. 6 p. 41619301 Lynn, S. (1990) Ames Mutagenicity Assay: Bioban P1487: Lab Project Number: 90G/0526. Unpublished study by Toxikon Corp. 14 p. 41619302 Griffin, T. (1990) Subchronic 90-Day Dermal Toxicity Study of Bio- ban P-1487 in Rats: Lab Project Number: 890202. Unpublished study prepared by Coulston International, Inc. 311 p. 41673801 Griffin, T. (1990) A Teratology Study of Bioban P-1487 in Rats: Final Report: Lab Project Number: 890402. Unpublished study prepared by Coulston International, Inc. 84 p. 41 ------- 41677602 Kreuzmann, B. (1990) Acute Dermal Toxicity in Rabbits—Median Lethal Dosage Determination: Lab Project Number: 90-4091-21 (B). Unpublished study prepared by Hill Top Laboratories, Inc. 109 p. 41677603 Kreuzmann, B. (1990) Primary Eye Irritation Study in Rabbits: Bioban P-1487: Lab Project Number: 90-4091-21 (D). Unpublished study prepared by Hill Top Laboratories, Inc. 14 p. 41677604 Kreuzmann, B. (1990) Primary Skin Irritation Study in Rabbits: Bioban P-1487: Lab Project Number: 90-4091-21 (C). Unpublished study prepared by Hill Top Laboratories, Inc. 14 p. 41810802 Kreuzmann, J. (1990) Primary Skin Irritation Study in Rabbits: Lab Project Number: 90-4091-21 (C). Unpublished study prepared by Hill Top Biolabs, Inc. 31 p. 41978802 Griffin, T. (1991) Supplemental Data to MRID No. 41673801: A Teratology Study of Bioban P-1487 in Rats. Unpublished study prepared by Consulton International, Inc. 12 p. 41995101 Bollmeier, A. (1990). Product Chemistry for Bioban P-1487. Unpublished study prepared by Angus Chemical Co. 28 p. 42440001 Griffin, T. (1992) Subchronic 90-day Dermal Toxicity Study of Bioban P-1487 in Rats (Limit Test): Lab Project Number: 910302. Unpublished study prepared by Coulston Research, Inc. 228 p. 43494001 Burke, B. (1994) Hydrolyses of 4-(2-Nitrobutyl) morpholine and 4,4'-(2-Ethyl-2- nitrotrimethylene)dimorpholine: Lab Project Number: PRT-23-4ANN-01: PRT-23-4ANN-01-003. Unpublished study prepared by Plant Research Technologies, Inc. 149 p. 43558901 Fitzgerald, G. (1995) Acute Oral Toxicity Study (in Rats): Bioban P-1487: Final Report: Lab Project Number: 94G-1937. Unpublished study prepared by Toxikon Corp. 18 p. 45655301 Linscombe, V.A., M.R. Schisler, and K.F. Treadway (2002) Evaluation of Bioban P-1487 in the mouse lymphoma (L5178Y TK +/-) forward mutation assay: Toxicology and Environmental Research and Consulting, Dow Chemical Company, Midland, MI, Laboratory ID 011110. 45900901 Estimating the Soil Koc for a Series of Biocides by HPLC Using OECD method 121 by S.J. Gonsoir, M.A. rivard, and M.K. Stock, 2002, Biocides TS and D, the Dow Chemical Company, Midland, Michigan. 42 ------- 46965903 Cifone, M.A. (2002) In vivo/in vitro unscheduled DNA synthesis in rat primary hepatocyte cultures at two time points with a dose range-finding assay with Bioban P-1487: Covance Laboratories, VA, Study No. 23622-0-494, Dow No. 021036, August 25, 2002. 47005501 Spencer, PJ. (2003) Evaluation of Bioban P-1487 in the mouse bone marrow micronucleus test. Toxicology and Environmental Research and Consulting, Dow, Midland, MI, Study 020146, March 14, 2003. 47005502 Gonsior, S.; Stock, M.; Rivard, M. (2002) Evaluation of the Ready Biodegradability of Bioban P-1487 Biocide using the OECD Method 301F: Manometric Respirometry Test. Project Number: 011131. Unpublished study prepared by Dow Chemical Co. 31 p. 47005504 Kirk, H.D., Staley, J.L., McClymont, E.L., and McFadden, L.G. 2002. Bioban P- 1487: Growth Inhibition test with the Freshwater Green Alga, Selenastrum capricornutum Printz. Study No. 021001. Conducted by Toxicology & Environmental Research and Consulting, The Dow Chemical Company. 93055001 Fink, R. and Beavers, IB. 1990. Bioban P-1487: An Acute Oral Toxicity Study with the Mallard Duck. Project No. 170-103. Conducted by Wildlife International, LTD. 93055002 Fink, R. and Beavers, J.B. 1990. Bioban P-1487; Eight-day Dietary LC50 in Bobwhite Quail. Project No. 170-101. Conducted by Wildlife International, LTD MRID 93055003. Fink, R. and Beavers, J.B. 1990. Bioban P-1487: Eight-day Dietary LC50 in Bobwhite Quail. Project No. 170-102. Conducted by Wildlife International. LTD. 93055004 Griffen, J. and Thompson, C.M. 1980. Acute Toxicity of Bioban P-1487 to Bluegill Sunfish (Lempomis machrochirus). Project No. 25061. Conducted by Analytical Bio Chemistry Laboratories. 93055005 Griffen, J. and Thompson, C.M. 1980. Acute Toxicity of Bioban P-1487 to the Rainbow Trout (Salmo gairdneri). Project No. 25145 Conducted by Analyical Bio Chemistry Laboratories. 43 ------- Supporting Documentation A Memo from Roxolana Kashuba to Steven Bradburry, Director EFED, April 2006 Dang. 1997. The Use of Models for Estimating Exposure and Risk of Antimicrobials in Metalworking Fluids. AAMAMWF Symposium, September 15-19, 1998. The Estimation Programs Interface (EPI) Suite. Windows based suite of physical/chemical properties and environmental estimation models developed by the US EPA's Office of Prevention, Pesticides, and Toxic Substances (OPPTS) and Syracuse Research Institute (SRC), http://www.epa.gov/opptintr/exposure/docs/EPISuitedl.htm FDA. 2003, A Guidance For Industry: Preparations of Food Contact Notifications and Food Additive Petitions for Food Contact Substances, Chemistry Recommendations. Final Guidance, April 2003. http://www.cfsan.fda.gov FDA. 2003. Sanitizing Solutions: Chemistry Guidance for Food Additive Petitions, January 2003. http://www.cfsan.fda.gov SEVIetric. 2005. Mass, Weight, Density, or Specific Gravity of Bulk Materials. http://www.simetric.co.ulc/si_materials.htm, last accessed February 2007. U.S. Environmental Protection Agency (EPA). 1992. A Laboratory Method to Determine the Retention of Liquids on the Surface of Hands. Prepared by C. Cinalli, C. Carter, A. Clark, and D. Dixon, under EPA Contract No. 68-02-4254. EPA-747/R-92-003. Exposure Evaluation Division, Office of Pollution Prevention and Toxics. September 1992. U.S. Environmental Protection Agency (EPA). 1997. Exposure Factors Handbook. Volume I-II. Office of Research and Development. Washington, D.C. EPA/600/P-95/002Fa. U.S. Environmental Protection Agency (EPA). 1998. PHED Surrogate Exposure Guide. Estimates of Worker Exposure from the Pesticide Handler Exposure Database Version 1.1. Washington, DC: U.S. Environmental Protection Agency. U.S. Environmental Protection Agency (EPA). 1999. Chemical Manufacturers Association Antimicrobial Exposure Study. Washington, DC. DP Barcode D247642. U.S. Environmental Protection Agency (EPA). 2002. Bioban P-1487 - Report of the Antimicrobials Division Toxicology Endpoint Selection Committee. Revised on January 25, 2007. 44 ------- Appendix E. Generic Data Call-In The Agency intends to issue a Generic Data Call-In at a later date. See Chapter V of the Bioban P-1487 RED for a list of studies that the Agency plans to include in the Generic Data Call-in. 45 ------- Appendix F. Product Specific Data Call-In The Agency intends to issue a Product Specific Data Call-In at a later date. 46 ------- Appendix G. Batching of Bioban P-1487 Products for Meeting Acute Toxicity Data Requirements for Reregistration The Agency will complete the batching for Bioban P-1487 at a later date. 47 ------- Appendix H. List of All Registrants Sent the Data Call-In A list of registrants sent the data call-in will be posted at a later date. 48 ------- Appendix I. List of Available Related Documents and Electronically Available Forms Pesticide Registration Forms are available at the following EPA internet site: http://www.epa.gov/opprd001/forms/. Pesticide Registration Forms (These forms are in PDF format and require the Acrobat reader) Instructions 1. Print out and complete the forms. (Note: Form numbers that are bolded can be filled out on your computer then printed.) 2. The completed form(s) should be submitted in hardcopy in accord with the existing policy. 3. Mail the forms, along with any additional documents necessary to comply with EPA regulations covering your request, to the address below for the Document Processing Desk. DO NOT fax or e-mail any form containing 'Confidential Business Information' or 'Sensitive Information.' If you have any problems accessing these forms, please contact Nicole Williams at (703) 308- 5551 or by e-mail atwilliams.nicole@epamail.epa.gov. The following Agency Pesticide Registration Forms are currently available via the internet at the following locations: 8570-1 8570-4 8570-5 8570-17 8570-25 8570-27 8570-28 8570-30 8570-32 8570-34 8570-35 8570-36 8570-37 Application for Pesticide Registration/Amendment Confidential Statement of Formula Notice of Supplemental Registration of Distribution of a Registered Pesticide Product Application for an Experimental Use Permit Application for/Notification of State Registration of a Pesticide To Meet a Special Local Need Formulator's Exemption Statement Certification of Compliance with Data Gap Procedures Pesticide Registration Maintenance Fee Filing Certification of Attempt to Enter into an Agreement with other Registrants for Development of Data Certification with Respect to Citations of Data (in PR Notice 98-5) Data Matrix (in PR Notice 98-5) Summary of the Physical/Chemical Properties (in PR Notice 98-1) Self-Certification Statement for the Physical/Chemical Properties (in PR Notice 98-1) http://www.epa.sov/opprd001/forms/8570-l.pdf http://www.epa.sov/opprd001/forms/8570-4.pdf http://www.epa.sov/opprd001/forms/8570-5.pdf http://www.epa.sov/opprd001/forms/8570-17.pdf http://www.epa.sov/opprd001/forms/8570-25.pdf http://www.epa.sov/opprd001/forms/8570-27.pdf http://www.epa.sov/opprd001/forms/8570-28.pdf http://www.epa.sov/opprd001/forms/8570-30.pdf http://www.epa.sov/opprd001/forms/8570-32.pdf http://www.epa.sov/opppmsdl/PR Notices/pr98- 5.pdf http://www.epa.sov/opppmsdl/PR Notices/pr98- 5.pdf http://www.epa.sov/opppmsdl/PR Notices/pr98- l.pdf http://www.epa.sov/opppmsdl/PR Notices/pr98- l.pdf 49 ------- Pesticide Registration Kit www.epa.gov/pesticides/registrationkit/. Dear Registrant: For your convenience, we have assembled an online registration kit that contains the following pertinent forms and information needed to register a pesticide product with the U.S. Environmental Protection Agency's Office of Pesticide Programs (OPP): 1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug and Cosmetic Act (FFDCA) as Amended by the Food Quality Protection Act (FQPA) of 1996. 2. Pesticide Registration (PR) Notices a. 83-3 Label Improvement Program—Storage and Disposal Statements b. 84-1 Clarification of Label Improvement Program c. 86-5 Standard Format for Data Submitted under FIFRA d. 87-1 Label Improvement Program for Pesticides Applied through Irrigation Systems (Chemigation) e. 87-6 Inert Ingredients in Pesticide Products Policy Statement f. 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement g. 95-2 Notifications, Non-notifications, and Minor Formulation Amendments h. 98-1 Self Certification of Product Chemistry Data with Attachments (This document is in PDF format and requires the Acrobat reader.) Other PR Notices can be found at http://www.epa.gov/opppmsdl/PR_Notices. 3. Pesticide Product Registration Application Forms (These forms are in PDF format and will require the Acrobat reader.) a. EPA Form No. 8570-1, Application for Pesticide Registration/Amendment b. EPA Form No. 8570-4, Confidential Statement of Formula c. EPA Form No. 8570-27, Formulator's Exemption Statement d. EPA Form No. 8570-34, Certification with Respect to Citations of Data e. EPA Form No. 8570-35, Data Matrix 50 ------- 4. General Pesticide Information (Some of these forms are in PDF format and will require the Acrobat reader.) a. Registration Division Personnel Contact List b. Biopesticides and Pollution Prevention Division (BPPD) Contacts c. Antimicrobials Division Organizational Structure/Contact List d. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements (PDF format) e. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF format) f. 40 CFR Part 158, Data Requirements for Registration (PDF format) g. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27, 1985) Before submitting your application for registration, you may wish to consult some additional sources of information. These include: 1. The Office of Pesticide Programs' Web Site 2. The booklet "General Information on Applying for Registration of Pesticides in the United States", PB92-221811, available through the National Technical Information Service (NTIS) at the following address: National Technical Information Service (NTIS) 5285 Port Royal Road Springfield, VA 22161 The telephone number for NTIS is (703) 605-6000. Please note that EPA is currently in the process of updating this booklet to reflect the changes in the registration program resulting from the passage of the FQPA and the reorganization of the Office of Pesticide Programs. We anticipate that this publication will become available during the Fall of 1998. 3. The National Pesticide Information Retrieval System (NPIRS) of Purdue University's Center for Environmental and Regulatory Information Systems. This service does charge a fee for subscriptions and custom searches. You can contact NPIRS by telephone at (765) 494-6614 or through their Web site. 4. The National Pesticide Information Center (NPIC) can provide information on active ingredients, uses, toxicology, and chemistry of pesticides. You can contact NPTN by telephone at (800) 858-7378 or through their Web site: http://npic.orst.edu/ The Agency will return a notice of receipt of an application for registration or amended registration, experimental use permit, or amendment to a petition if the applicant or petitioner 51 ------- encloses with his submission a stamped, self-addressed postcard. The postcard must contain the following entries to be completed by OPP: Date of receipt EPA identifying number Product Manager assignment Other identifying information may be included by the applicant to link the acknowledgment of receipt to the specific application submitted. EPA will stamp the date of receipt and provide the EPA identifying File Symbol or petition number for the new submission. The identifying number should be used whenever you contact the Agency concerning an application for registration, experimental use permit, or tolerance petition. To assist us in ensuring that all data you have submitted for the chemical are properly coded and assigned to your company, please include a list of all synonyms, common and trade names, company experimental codes, and other names which identify the chemical (including "blind" codes used when a sample was submitted for testing by commercial or academic facilities). Please provide a CAS number if one has been assigned. 52 ------- |