United States Environmental Protection Agency

1. United States Environmental Protection Agency ANTIMICROBIALS DIVISION Frank Sanders, Director

2. Topics to be Discussed • Background • International Activities • Changing Trends & Issues in the U.S. • Metal Working Fluids • Use of Structural Activity Relationship Process • Antifoulant Paints • Shock Policy • Pressure Treated Wood • Green Seal/Design for the Environment • Mold Policy

3. BACKGROUND

4. Background on EPA Regulatory Program • Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) requires EPA to register pesticide products, including antimicrobial pesticide products, for sale and distribution in the United States • EPA’s Antimicrobial Division is responsible for registering Antimicrobial Pesticides

5. Applicable Statutes Food Quality Protection Act (FQPA) Pesticide Registration Improvement Act (PRIA) Federal Food Drug And Cosmetic Act (FFDCA) Federal Insecticide Fungicide And Rodenticide Act (FIFRA) Tolerance Established Product Registered

6. Primary Functions Under FIFRA Manage the registration of pesticide products under the Federal Insecticide, Fungicide and Rodenticide Act • Pesticide registration (section 3) • New Chemicals • New Uses • Amendment • Old Chemical

7. AD Organizational Structure

8. Area of ResponsibilityAntimicrobials under FIFRA AD: Non AD: The Antimicrobials Division regulates chemicals used in or on environmental surfaces, as well as in air or in water, they include: Excluded from AD jurisdiction are:

9. AD Scope of Work • Currently there are more 200 active ingredients (Charted below) • Also, more than 5,000 products are registered with AD • Roughly 60% are public health products • More than 3.3 billion pounds used/yr (includes chlorine water treatment)

10. Major Outputs • Annually AD registers about: • 2 New Chemicals • 6 New Uses • 150 New Products • 900 Amendments • 500 Notifications • Annually AD also must issue about 4-10 RED’s per year until 2008 (then registration review begins)

11. Other Areas of Responsibility • AD also has the lead for: • Antimicrobial Homeland Security Coordination; • Antimicrobials Testing Program; • OECD Biocides Initiatives; • NAFTA Biocides Harmonization Initiatives; • 158W Data Requirement development; • Wood Preservatives (CCA, Pentachlorophenol and Creosote) • Antifoulants • And More….

12. INTERNATIONAL ACTIVITIES

13. International Coordination • EPA’s Antimicrobial Program continues to enjoy a growing working relationship with its international counterparts. • Most activities are coordinated with or through the following organizations/initiatives: • European Union (EU) • North America Free Trade Agreement (NAFTA) • Organization for Economic Cooperation and Development (OECD)

14. OECD Projects • Draft Test Guidelines for Leaching of Wood Preservatives from Treated Wood • The objective is to develop test guidelines that all countries can use in evaluating wood preservatives. EPA will be presenting its concerns during the Task Force meeting today. • Harmonization of Efficacy Test Methods for Antimicrobials used on Hard Surfaces and in Treated Articles • The objective is to develop harmonized test methods and performance standards for biocides used on hard surfaces and in treated articles. • The contractor presented a revised report to the Steering Group and it is envisioned that focus will be placed on the hard surface disinfectant for now. • Use of Biocides for Ships’ Ballast Water • AD is participating in an OECD discussion of work currently in progress in government and industry to address ballast water issues. • The TFB will consider whether they should be providing input in the broad arena of ballast water issues.

15. OECD Projects • Use of Biocides for Biosecurity • This is an area that has been opened up for the consideration of approaches to possibly evaluate efficacy testing of biocides which could be used to counter biosecurity threats. • AD worked with others to prepare a white paper providing a summary of the issues associated with the development, efficacy testing and registration of biocidal products to counter threats posed by biowarfare agents • Emission Scenario Documents (ESDs) for: Insecticides Used in Stables and Manure • The Agency determined these ESDs would be of low priority because they are dealing with insecticides and not biocides after the proposal was made at the 2003 TFB Meeting. • AD has been invited by the TFB coordinator of this project to review and comment. It has been explained to the OECD these are of low priority.

16. CHANGING TRENDS & ISSUES IN THE U.S.

17. Metal Working Fluids • The Agency is re-examining the toxicology data requirements to determine if a “tiered approach” is appropriate for MWF. • For closed systems with robust labeling restrictions, the Agency may register the product and conditionally require certain exposure data, if necessary. • Cancer studies may be held in reserve depending on the outcome of exposure data.

18. Metal Working Fluids • Data Requirements are substantially different if used in an open system vs. an enclosed system • What is an “enclosed System” • Enclosed metalworking systems are defined as systems in which the metalworking machine or process is enclosed by a box or housing. Openings in the enclosure are limited to the minimum required to allow for part entry/egress, maintenance, or utility access. • The enclosure is provided with exhaust ventilation with the replacement air entering through the openings designed into the enclosure.

19. Enclosed System (cont.) The enclosure of the machine or process is designed to surround the machining operation such that when MWF aerosol is emitted from the machining operation, it is already contained within the enclosure, thereby isolating the operation from the employee and the workplace. The aerosol is prevented from release at required enclosure openings by an inward flow of air generated by a slight negative pressure. Negative pressure is produced by extraction of air from the enclosure via a local exhaust ventilation system. Metal Working Fluids

20. Metal Working Fluids • When a registrant modifies his/her labeling to allow use of the proposed product for use only in “enclosed ‘metalworking systems”, then the Agency is willing to consider “reserving” certain toxicology data requirements • i.e., chronic, second developmental, and reproductive data -- pending registrant submission and Agency review of worker exposure data for “enclosed MWF system

21. Acute oral toxicity - rat Acute dermal toxicity Acute inhalation toxicity – rat Primary eye irritation - rabbit Primary dermal irritation Dermal sensitization Acute neurotoxicity - rat Subchronic Testing 90-Day oral toxicity - rodent 90-Day oral toxicity - non-rodent 21/28-Day dermal toxicity 90-Day dermal toxicity 90-Day inhalation - toxicity - rat 90-Day neurotoxicity - rat Chronic Testing Chronic toxicity - rodent Chronic toxicity - non-rodent Carcinogenicity - rat preferred Carcinogenicty - mouse preferred Developmental Toxicity and Reproduction Prenatal developmental toxicity - rat preferred Prenatal developmental toxicity - rabbit preferred Prenatal developmental toxicity - dermal Data Requirements for an Open System

22. Reproduction and fertility effects Developmental neurotoxicity Mutagenicity Bacterial reverse mutation assay In vitro mammalian gene mutation In vivo cytogenetics (mutagenicity) Special Testing Metabolism and pharmacokinetics Companion animal safety Dermal penetration Scheduled controlled operant behavior Peripheral nerve function Neurophysiology: sensory evoked potentials Immunotoxicity Worker Exposure Data Exposure/monitoring study Product use and description of human activity information Dermal/inhalation exposures information during application and post-application scenarios Data Requirements for an Open System

23. Use of Structural Activity Relationship Process for Risk Assessments • There is flexibility in FIFRA that allows the agency to consider other ways to assess risks without using FIFRA guideline studies. • We believe there is a scientific credible and defensible way to assess risk based on the way others within the agency assess non pesticide risks. • One way this has been done is by using the Structural Activity Relationship (SAR) process • In this process the chemical’s structural similarity to other similar chemicals, for which data is available, is used to determine toxicity

25. Chemical Structure Activity Relationships

26. Chemical Structure Activity Relationships

27. OPP’s Pesticide Risk Assessment Process: SAR • With respect to pesticide chemical assessment, SAR is most appropriately used when addressing dietary risk such as evaluating hard surface, food contact disinfectants where residues are generally less than 200ppb. • In this case the Agency may revise its tier one data requirements to include a literature search and a SAR analysis.

28. Tier 1 Data Adjustment • 90 day oral subchronic, rodent • 1 developmental study • Mutagenicity testing battery • Added data: Literature search • SAR

29. Data Requirement Adjustment • Depending on the outcome of the review of the literature search and SAR analysis, the following data will be held in reserve: • 90-day subchronic oral study, non-rodent • 2-generation reproduction study • Other studies as warranted from concerns raised in the literature search/SAR

30. Where Can SARs Data Be Used? • EPA can use SARs analysis data in areas where little data exist – such in the indirect food use arena • EPA data requirements for indirect food additives • Estimated daily intake <200 ppb • Estimated daily intake >200 ppb

31. What is an antimicrobial food use? • Direct application to food (not processed food) • Product not applied directly to food, but is used in such a way that food may reasonably be expected to bear inadvertent residues through indirect contact with a treated surface or substance

32. Commercial Food Processing Equipment Deli equipment Dairy Equipment Milk lines Field Washes Application to animal drinking water Animal premise treatment (now non-food but may be revisited in the future) Consumer Kitchen counter tops Microwaves Refrigerators Stove tops Tables High chairs Fruit and vegetable rinses Examples of Antimicrobial Food Uses

33. EPA Indirect Food Data Requirements (<200 ppb) • Mutagenicity battery • Subchronic oral toxicity test in rodent species • Developmental toxicity study • SAR • Literature search

34. Reserved Toxicity Testing • Reserve studies pending results of SAR, Lit search and Tier 1 review • Subchronic oral toxicity test in non-rodent species (dog) • 2-Generation reproductive toxicity test

35. EPA Indirect Food Data Requirements (>200 ppb) • All data below 200 ppb, plus • 2 carcinogenicity studies • 2 chronic feeding studies • Developmental toxicity study in second species • Metabolism study

36. Recent developments in toxicity testing • Literature search • SAR • Mutagenicity battery • Subchronic oral toxicity study in rodent species

37. Antifoulant Paint Use Alternatives for TBT • AD has expedited new registration applications for antifoulant paint products intended to replace TBT products. • Most TBT antifoulant products are now cancelled. • EPA is continuing its discussions with NAVSEA (Naval Sea Systems Command) regarding new antifoulant paints that might fit their needs. • These types of initiatives should provide more protection to the ecological environment.

38. Defining the Term “Shock” for Swimming Pools • What does the term shock mean? • Is it a pesticide claim? • Is it a non pesticide claim? • Is it both a pesticide claim and a non pesticide claim? • Does the term Shock apply to swimming pools, hot tubs, spas and drinking water wells

39. Defining the Term “Shock” for Swimming Pools • Preliminary Determination • AD discuss these questions with Industry, Health Care Professionals, State Representatives, EPA Regions and a host of others. Most believe that the term shock should be considered a pesticide claim. • The manufacturers of the chemical that is used for water clarity agreed with the Agency’s proposed new term “shock oxidizer” and would consider this term a non pesticide claim. • An Enforcement Alert has been developed as well as notification that will appear on the EPA web page.

40. Sodium Bromide in Pools and Spas • AD is concerned about outdoor pool applications of sodium bromide – it appears that bromate is formed • AD’s concern is based on data recently submitted • There is limited data on bromate concentration in pools from application of sodium bromide • Sodium bromate indoor swimming pool and spa applications are not a significant concern based on the lack of UV light • AD is awaiting confirmatory data to support this assumption

41. Data Requirements for Wood Preservatives • Data needed to assess Cr +6 risk. • 1) Data from a study which measures and speciates the levels of chromium on the surface of wood treated with ACC. • A. Hand wipe study which measured levels of arsenic and Cr(III) and Cr(VI). The surface residue also must be evaluated to determine whether trivalent chromium will oxidize into hexavalent chromium under reasonable use conditions. • 2. Data regarding the levels of exposure and the valence state of the chromium from both the inhalation and dermal routes to workers treating wood with ACC as well as those persons in the treatment plants who come in contact with treated wood or otherwise are exposed to chromium.

43. Data Requirements for Wood Preservatives • Subsequently, we determined that we only wanted the inhalation exposure data. It is the agency general policy (AD and HED) to require PPE (gloves, long pants, long sleeved shirts) when a chemical is a dermal irritant and/or sensitizer. • 3. Data on the form and quantity of the preservative chemical residue (copper, trivalent and hexavalent chromium) released into the environment, and the fate of the released compounds will also be needed in order to confirm the results of our ecotoxicity assessment. • We originally required these data. However, we are satisfied with the use of the existing data for CCA. • 4. Data on the conditions under which the Cr (VI ) in the ACC treating solution reduces to Cr ( III ) in the wood.

44. Typical Human Exposure Scenarios for Pressure Treated Wood Wood Preservatives • Application: • Pressure-treatment, thermal treatment, spraying, dipping, brushing, mixing/loading (dermal/inhalation) • Post-application: • Handling treated wood products (occupational – dermal/inhalation) • Contact with treated wood products (children: dermal, incidental oral)

45. Green Seal/Design for the Environment • The Agency has been approached by various registrants who would like to place the Green Seal on their product labeling • Green Seal is non-profit organization that charges a fee to assess whether or not a product meets its standards for being safe for the environment • The Agency’s claim board has not permitted the request because EPA’s regulations do not allow the following: • Logos cannot be false or misleading • No implied safety claims allowed • No comparative statements allowed • However, the Agency is looking at considering working with its Design for the Environment Program (OPPT) to find ways to help consumers identify reduced risk pesticides in the marketplace

46. Mold Policy – Hurricane Katrina • The Agency does not require submission of efficacy data for products making claims to control mod and mildew. • The submission of efficacy data is required if the applicant lists a fungal species on the label. • Most of these products were registered to control mold growth for aesthetic purposes. • Registrants making residual or prevention claims have the following options: • Submit efficacy data to support claim • Delete mold claim from the label • AD has also been working with States recovering from Hurricane Katrina to provide guidance on dealing with the enormous issue of mold in the flooded areas of Mississippi and Louisiana

47. Other Issues Include…. • Norwalk Virus • Bio-terrorism -- Anthrax • Quantitative Carrier Testing II (QCT2) • Heating and Ventilation/ Air Conditioning (HVAC) Issues • Treated Articles • Material Surface Safety • 158(W) • Ballast Water: New Use Site • Biofilm protocols/registration: Dental unit water lines/hard surface disinfectant

48. Other Issues Include…. • Level Playing Field compliance issues • Company “A” complies with registration requirements – company “B” is in the marketplace with unregistered product making the same claims as company “A” • Barrier Claims • Endangered Species • PRIONS • Medical Waste • Nail Salon Outbreaks… and more…

49. In Conclusion • The world of antimicrobials is and will continue to push the bounds of present methodologies and science policies • In keeping pace with this ever changing market the Agency will continue to work closely with all its stakeholders and seek to understand all points of view so that it may continue to reap the benefit of an open and inclusive decision-making process